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Mendeliome v1.963 NUDCD2 Seb Lunke Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1867 SART3 Daniel Flanagan gene: SART3 was added
gene: SART3 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: SART3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SART3 were set to PMID: 37296101
Phenotypes for gene: SART3 were set to Neurodevelopmental disorder (MONDO#0700092), SART3-related; 46,XY disorder of sex development (MONDO:0020040), SART3-related
Review for gene: SART3 was set to GREEN
Added comment: Nine individuals from six families presenting with intellectual disability, global developmental delay, a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Additionally, two individuals had seizures and two had epileptiform activity reported on EEG.

Human induced pluripotent stem cells carrying patient variants in SART3 show disruption to multiple signalling pathways, upregulation of spliceosome components and demonstrate aberrant gonadal and neuronal differentiation in vitro.
Sources: Expert list
Mendeliome v1.963 NUDCD2 Seb Lunke Classified gene: NUDCD2 as Amber List (moderate evidence)
Mendeliome v1.963 NUDCD2 Seb Lunke Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5256 SART3 Krithika Murali Classified gene: SART3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5256 SART3 Krithika Murali Gene: sart3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1867 RPH3A Elena Savva Classified gene: RPH3A as Green List (high evidence)
Genetic Epilepsy v0.1867 RPH3A Elena Savva Gene: rph3a has been classified as Green List (High Evidence).
Mendeliome v1.962 NUDCD2 Ee Ming Wong gene: NUDCD2 was added
gene: NUDCD2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUDCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDCD2 were set to 37272762
Phenotypes for gene: NUDCD2 were set to Multiple congenital anomalies (MONDO:0019042), NUDCD2-related
Penetrance for gene: NUDCD2 were set to unknown
Review for gene: NUDCD2 was set to AMBER
gene: NUDCD2 was marked as current diagnostic
Added comment: - Two unrelated probands, each biallelic for two variants in NUDCD2 (total 3x LoF variants, 1x missense variant)
- Immunoblotting of proteins extracted from the primary fibroblasts of one proband with 2x LoF variants demonstrated markedly reduced NUDCD2 levels compared to healthy individuals
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5255 SART3 Krithika Murali Marked gene: SART3 as ready
Intellectual disability syndromic and non-syndromic v0.5255 SART3 Krithika Murali Gene: sart3 has been removed from the panel.
Genetic Epilepsy v0.1866 RPH3A Elena Savva Classified gene: RPH3A as Green List (high evidence)
Genetic Epilepsy v0.1866 RPH3A Elena Savva Gene: rph3a has been classified as Green List (High Evidence).
Fetal anomalies v1.119 NUDCD2 Seb Lunke Marked gene: NUDCD2 as ready
Fetal anomalies v1.119 NUDCD2 Seb Lunke Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5255 RPH3A Elena Savva Classified gene: RPH3A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5255 RPH3A Elena Savva Gene: rph3a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1866 RPH3A Elena Savva Classified gene: RPH3A as Green List (high evidence)
Genetic Epilepsy v0.1866 RPH3A Elena Savva Gene: rph3a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5255 RPH3A Elena Savva Classified gene: RPH3A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5255 RPH3A Elena Savva Gene: rph3a has been classified as Green List (High Evidence).
Fetal anomalies v1.119 NUDCD2 Seb Lunke Classified gene: NUDCD2 as Amber List (moderate evidence)
Fetal anomalies v1.119 NUDCD2 Seb Lunke Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1865 RPH3A Elena Savva Marked gene: RPH3A as ready
Genetic Epilepsy v0.1865 RPH3A Elena Savva Gene: rph3a has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.5254 RPH3A Elena Savva Marked gene: RPH3A as ready
Intellectual disability syndromic and non-syndromic v0.5254 RPH3A Elena Savva Gene: rph3a has been removed from the panel.
Callosome v0.497 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Fetal anomalies v1.118 NUDCD2 Ee Ming Wong gene: NUDCD2 was added
gene: NUDCD2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NUDCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDCD2 were set to 37272762
Phenotypes for gene: NUDCD2 were set to Multiple congenital anomalies (MONDO:0019042), NUDCD2-related
Penetrance for gene: NUDCD2 were set to unknown
Review for gene: NUDCD2 was set to AMBER
gene: NUDCD2 was marked as current diagnostic
Added comment: - Two unrelated probands, each biallelic for two variants in NUDCD2 (total 3x LoF variants, 1x missense variant)
- Immunoblotting of proteins extracted from the primary fibroblasts of one proband with 2x LoF variants demonstrated markedly reduced NUDCD2 levels compared to healthy individuals
Sources: Literature
Callosome v0.497 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Mendeliome v1.962 DCAF13 Seb Lunke Marked gene: DCAF13 as ready
Mendeliome v1.962 DCAF13 Seb Lunke Gene: dcaf13 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.238 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Skeletal dysplasia v0.238 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Mendeliome v1.962 RAB34 Elena Savva Marked gene: RAB34 as ready
Mendeliome v1.962 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Mendeliome v1.962 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Mendeliome v1.962 DCAF13 Seb Lunke Classified gene: DCAF13 as Red List (low evidence)
Mendeliome v1.962 DCAF13 Seb Lunke Gene: dcaf13 has been classified as Red List (Low Evidence).
Callosome v0.496 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Mendeliome v1.962 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Mendeliome v1.962 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Fetal anomalies v1.118 RAB34 Elena Savva Marked gene: RAB34 as ready
Fetal anomalies v1.118 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Growth failure v1.64 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Growth failure v1.64 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Fetal anomalies v1.118 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Fetal anomalies v1.117 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Fetal anomalies v1.117 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.237 DRG1 Krithika Murali Marked gene: DRG1 as ready
Skeletal dysplasia v0.237 DRG1 Krithika Murali Gene: drg1 has been removed from the panel.
Clefting disorders v0.198 RAB34 Elena Savva Marked gene: RAB34 as ready
Clefting disorders v0.198 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Clefting disorders v0.198 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Callosome v0.496 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Callosome v0.496 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Clefting disorders v0.197 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Clefting disorders v0.197 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Callosome v0.495 RAB34 Elena Savva Marked gene: RAB34 as ready
Callosome v0.495 RAB34 Elena Savva Gene: rab34 has been removed from the panel.
Radial Ray Abnormalities v1.9 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Growth failure v1.63 DRG1 Krithika Murali Marked gene: DRG1 as ready
Growth failure v1.63 DRG1 Krithika Murali Gene: drg1 has been removed from the panel.
Skeletal dysplasia v0.237 DRG1 Dean Phelan gene: DRG1 was added
gene: DRG1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRG1 were set to PMID: 37179472
Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related
Review for gene: DRG1 was set to GREEN
Added comment: PMID: 37179472
- Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function.
Sources: Literature
Radial Ray Abnormalities v1.8 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Radial Ray Abnormalities v1.7 RAB34 Elena Savva Marked gene: RAB34 as ready
Radial Ray Abnormalities v1.7 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Growth failure v1.63 DRG1 Krithika Murali Marked gene: DRG1 as ready
Growth failure v1.63 DRG1 Krithika Murali Gene: drg1 has been removed from the panel.
Radial Ray Abnormalities v1.7 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Radial Ray Abnormalities v1.7 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Microcephaly v1.209 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Microcephaly v1.209 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Microcephaly v1.209 DRG1 Krithika Murali Marked gene: DRG1 as ready
Microcephaly v1.209 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Microcephaly v1.209 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Microcephaly v1.209 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Microcephaly v1.208 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Microcephaly v1.208 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Radial Ray Abnormalities v1.6 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Radial Ray Abnormalities v1.6 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Microcephaly v1.208 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Microcephaly v1.208 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Microcephaly v1.207 DRG1 Dean Phelan gene: DRG1 was added
gene: DRG1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRG1 were set to PMID: 37179472
Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related
Review for gene: DRG1 was set to GREEN
Added comment: PMID: 37179472
- Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function.
Sources: Literature
Mendeliome v1.961 ARPC5 Paul De Fazio gene: ARPC5 was added
gene: ARPC5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARPC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARPC5 were set to 37349293; 37382373
Phenotypes for gene: ARPC5 were set to Combined immunodeficiency, ARPC5-related MONDO:0015131
Review for gene: ARPC5 was set to GREEN
gene: ARPC5 was marked as current diagnostic
Added comment: 4 individuals from 3 families reported with homozygous LoF variants. All had recurrent and severe infections. Other developmental anomalies were present but seemed variable.

PMID:37349293 reports 2 unrelated patients. Both had scoliosis. One had neurodevelopmental delay and brain atrophy. Patient 1 died at 15yo after a sudden episode of hemoptysis and hematochezia. Patient 2 died at 1yo because of progressive neurologic and respiratory disease; an autopsy was not performed.

PMID:37382373 reports 2 patients from the same family. One had multiple congenital anomalies including a congenital heart defect (CHD) (patent foramen ovale), cleft palate, and hypoplastic corpus callosum. The sibling also had CHD (moderate pulmonary stenosis and atrial septal defect).

Functional studies and a mouse model were supportive of the disease association.
Sources: Literature
Stroke v1.8 ANO1 Suliman Khan changed review comment from: Sources: Literature; to: PMID: 37253099: screening analysis of Moyamoya disease (MMD) cohort revealed 8 patients with variants in the ANO1 gene. Two families had the same rare variant p.Met658Val in ANO1 gene. The ANO1 rare variants were assessed using patch-clamp recordings, and the majority of variants, including ANO1 p.Met658Val, displayed increased sensitivity to intracellular Ca2+. Patients harboring these gain-of-function ANO1 variants had classic features of MMD, but also had aneurysm, stenosis, and/or occlusion in the posterior circulation.
Mendeliome v1.961 RPH3A Seb Lunke Marked gene: RPH3A as ready
Mendeliome v1.961 RPH3A Seb Lunke Gene: rph3a has been classified as Green List (High Evidence).
Stroke v1.8 ANO1 Suliman Khan gene: ANO1 was added
gene: ANO1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: ANO1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ANO1 were set to PMID: 37253099
Phenotypes for gene: ANO1 were set to moyamoya; cerebral arteriopathy; stroke; MONDO:0016820
Penetrance for gene: ANO1 were set to unknown
Review for gene: ANO1 was set to AMBER
Added comment: Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5254 SART3 Daniel Flanagan edited their review of gene: SART3: Changed phenotypes: Neurodevelopmental disorder (MONDO#0700092), SART3-related, 46,XY disorder of sex development (MONDO:0020040), SART3-related
Mendeliome v1.961 DRG1 Krithika Murali Marked gene: DRG1 as ready
Mendeliome v1.961 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Mendeliome v1.961 RPH3A Seb Lunke Classified gene: RPH3A as Green List (high evidence)
Mendeliome v1.961 RPH3A Seb Lunke Gene: rph3a has been classified as Green List (High Evidence).
Mendeliome v1.961 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Mendeliome v1.961 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.51 MIR204 Elena Savva Marked gene: MIR204 as ready
Cone-rod Dystrophy v0.51 MIR204 Elena Savva Gene: mir204 has been classified as Amber List (Moderate Evidence).
Growth failure v1.63 DRG1 Dean Phelan gene: DRG1 was added
gene: DRG1 was added to Growth failure. Sources: Literature
Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRG1 were set to PMID: 37179472
Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related
Review for gene: DRG1 was set to GREEN
Added comment: PMID: 37179472
- Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function.
Sources: Literature
Cone-rod Dystrophy v0.51 MIR204 Elena Savva Classified gene: MIR204 as Amber List (moderate evidence)
Cone-rod Dystrophy v0.51 MIR204 Elena Savva Gene: mir204 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.116 DRG1 Krithika Murali Marked gene: DRG1 as ready
Fetal anomalies v1.116 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Mendeliome v1.960 MIR204 Elena Savva Classified gene: MIR204 as Amber List (moderate evidence)
Mendeliome v1.960 MIR204 Elena Savva Gene: mir204 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.39 ARPC5 Paul De Fazio gene: ARPC5 was added
gene: ARPC5 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: ARPC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARPC5 were set to 37349293; 37382373
Phenotypes for gene: ARPC5 were set to Combined immunodeficiency, ARPC5-related MONDO:0015131
Review for gene: ARPC5 was set to GREEN
gene: ARPC5 was marked as current diagnostic
Added comment: 4 individuals from 3 families reported with homozygous LoF variants. All had recurrent and severe infections. Other developmental anomalies were present but seemed variable.

PMID:37349293 reports 2 unrelated patients. Both had scoliosis. One had neurodevelopmental delay and brain atrophy. Patient 1 died at 15yo after a sudden episode of hemoptysis and hematochezia. Patient 2 died at 1yo because of progressive neurologic and respiratory disease; an autopsy was not performed.

PMID:37382373 reports 2 patients from the same family. One had multiple congenital anomalies including a congenital heart defect (CHD) (patent foramen ovale), cleft palate, and hypoplastic corpus callosum. The sibling also had CHD (moderate pulmonary stenosis and atrial septal defect).

Functional studies and a mouse model were supportive of the disease association.
Sources: Literature
Fetal anomalies v1.116 DRG1 Krithika Murali Publications for gene: DRG1 were set to PMID: 37179472
Mendeliome v1.959 MIR204 Elena Savva Classified gene: MIR204 as Amber List (moderate evidence)
Mendeliome v1.959 MIR204 Elena Savva Gene: mir204 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.958 MIR204 Elena Savva Marked gene: MIR204 as ready
Mendeliome v1.958 MIR204 Elena Savva Gene: mir204 has been removed from the panel.
Fetal anomalies v1.115 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Fetal anomalies v1.115 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.50 MIR204 Chern Lim gene: MIR204 was added
gene: MIR204 was added to Cone-rod Dystrophy. Sources: Literature
Mode of inheritance for gene: MIR204 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MIR204 were set to 26056285; 37321975
Phenotypes for gene: MIR204 were set to Retinal dystrophy and iris coloboma with or without cataract (MIM#616722)
Mode of pathogenicity for gene: MIR204 was set to Other
Review for gene: MIR204 was set to AMBER
gene: MIR204 was marked as current diagnostic
Added comment: PMID: 26056285
- Bilateral coloboma and rod-cone dystrophy with or without cataract in nine individuals of a five-generation family.
- Heterozygous n.37C>T segregates with the disease in all affected individuals.
- Functional analysis including transcriptome analysis showed this variant resulted in significant alterations of miR-204 targeting capabilities. In vivo injection, in medaka fish (Oryzias latipes), of the mutated miR-204 caused a phenotype consistent with that observed in the family.
- Authors suggested gain of function is the likely disease mechanism.

PMID: 37321975
- Four members of a three-generation family with early-onset chorioretinal dystrophy, heterozygous for n.37C>T.
- Additionally, four family members were shown to be affected by albinism resulting from biallelic pathogenic OCA2 variants.
- Haplotype analysis excluded relatedness with the family reported in PMID: 26056285.
- In silico analysis of the MIR204 n.37C>T variant reveals profound changes to its target mRNAs and suggests a gain-of-function mechanism of miR 204 variant.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5254 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5254 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Optic Atrophy v1.18 MIR204 Elena Savva Marked gene: MIR204 as ready
Optic Atrophy v1.18 MIR204 Elena Savva Gene: mir204 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5253 DRG1 Krithika Murali Marked gene: DRG1 as ready
Intellectual disability syndromic and non-syndromic v0.5253 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Fetal anomalies v1.114 DRG1 Dean Phelan gene: DRG1 was added
gene: DRG1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRG1 were set to PMID: 37179472
Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related
Review for gene: DRG1 was set to GREEN
Added comment: PMID: 37179472
- Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5253 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5253 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Optic Atrophy v1.18 MIR204 Elena Savva Classified gene: MIR204 as Amber List (moderate evidence)
Optic Atrophy v1.18 MIR204 Elena Savva Gene: mir204 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v0.34 ANO1 Seb Lunke changed review comment from: Comment on list classification: This paper that indicates a predisposition, with both functional data and segregation data somewhat conflicting. Keep at amber for now as clear causality (consistent with author views) remains to be established.; to: Comment on list classification: This paper indicates a predisposition, with both functional data and segregation data somewhat conflicting. Keep at amber for now as clear causality (consistent with author views) remains to be established.
Cerebral vascular malformations v0.34 ANO1 Seb Lunke Marked gene: ANO1 as ready
Cerebral vascular malformations v0.34 ANO1 Seb Lunke Gene: ano1 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v0.34 ANO1 Seb Lunke Phenotypes for gene: ANO1 were changed from moyamoya; cerebral arteriopathy to Moyamoya disease, MONDO:0016820, ANO1 related
Cerebral vascular malformations v0.33 ANO1 Seb Lunke Classified gene: ANO1 as Amber List (moderate evidence)
Cerebral vascular malformations v0.33 ANO1 Seb Lunke Added comment: Comment on list classification: This paper that indicates a predisposition, with both functional data and segregation data somewhat conflicting. Keep at amber for now as clear causality (consistent with author views) remains to be established.
Cerebral vascular malformations v0.33 ANO1 Seb Lunke Gene: ano1 has been classified as Amber List (Moderate Evidence).
Radial Ray Abnormalities v1.5 RAB34 Sarah Pantaleo gene: RAB34 was added
gene: RAB34 was added to Radial Ray Abnormalities. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to PMID: 37384395
Phenotypes for gene: RAB34 were set to Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies
Penetrance for gene: RAB34 were set to Complete
Review for gene: RAB34 was set to GREEN
Added comment: Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogenous disorders characterised by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in >20 genes encoding ciliary proteins have been found to cause OFDS.

Identified by WES biallelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families (aided by GeneMatcher).

Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects.

RAB34 encodes a member of the Lab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Protein products of pathogenic variants clustered near the RAB34 C-terminus exhibit a strong loss of function.

Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, brain malformations), resulting in medical termination for three probands.

In the fourth, the only one alive at birth, proband born at 39+5 weeks, normal growth parameters after pregnancy with polyhydramnios, corpus callosum agenesis and polydactyly. Respiratory distress at birth.

All four probands presented typical features of ciliopathy disorders, overlapping with oral, facial and digital abnormalities.

All with homozygous missense variants. All absent in gnomAD (in homozygous state). Sanger sequencing confirmed mode of inheritance.
Sources: Literature
Mendeliome v1.958 DCAF13 Michelle Torres gene: DCAF13 was added
gene: DCAF13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DCAF13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DCAF13 were set to 36797467
Phenotypes for gene: DCAF13 were set to Neuromuscular disease (MONDO#0019056), DCAF13-related
Review for gene: DCAF13 was set to RED
Added comment: One consanguineous family, 4x individuals homozygous NM_015420.7(DCAF13)c.907 G > A; p.(Asp303Asn) (3x via WES and 1x via Sanger) with a neuromuscular disorder characterized by a waddling gait, limb deformities, muscular weakness and facial palsy.

In silicos analysis of mutant DCAF13 suggests that the amino acid change is deleterious and affects a ß-hairpin turn, within a WD40 domain of the protein which may decrease protein stability. Functional studies were not performed.

Previously, a heterozygous variant in DCAF13 with or without a heterozygous missense variant in CCN3, was suggested to cause inherited cortical myoclonic tremor with epilepsy. In addition, a heterozygous DCAF13 variant has been associated with autism spectrum disorder.
Sources: Literature
Mendeliome v1.958 ERI1 Elena Savva Marked gene: ERI1 as ready
Mendeliome v1.958 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Mendeliome v1.958 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Mendeliome v1.958 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Mendeliome v1.957 ERI1 Elena Savva gene: ERI1 was added
gene: ERI1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 37352860
Phenotypes for gene: ERI1 were set to Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related, Intellectual disability (MONDO#0001071), ERI1-related
Review for gene: ERI1 was set to GREEN
Added comment: PMID: 37352860 - 8 individuals from 7 unrelated families
- Patients with biallelic missense show a MORE severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly
- Patients with biallelic null/whole gene deletion had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly
- Patient chet for a missense and PTC variant has a blended phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, mild ID and failure to thrive

- Missense variants were functionally shown to not be able to rescue 5.8S rRNA processing in KO HeLa cells
- K/O mice had neonatal lethality with growth defects, brachydactyly. Skeletal-specific K/O had mild platyspondyly, had more in keeping with patients with null variants than missense

More severe phenotype hypothesised due to "exonuclease-dead proteins may compete for the target RNA molecules with other exonucleases that have functional redundancy
with ERI1, staying bound to those RNA molecules"
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5252 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5252 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5252 SART3 Daniel Flanagan gene: SART3 was added
gene: SART3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: SART3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SART3 were set to PMID: 37296101
Phenotypes for gene: SART3 were set to Neurodevelopmental disorder (MONDO#0700092), SART3-related, with 46,XY gonadal dysgenesis
Review for gene: SART3 was set to GREEN
Added comment: Nine individuals from six families presenting with intellectual disability, global developmental delay, a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Additionally, two individuals had seizures and two had epileptiform activity reported on EEG.

Human induced pluripotent stem cells carrying patient variants in SART3 show disruption to multiple signalling pathways, upregulation of spliceosome components and demonstrate aberrant gonadal and neuronal differentiation in vitro.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5252 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5252 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5251 ERI1 Elena Savva Marked gene: ERI1 as ready
Intellectual disability syndromic and non-syndromic v0.5251 ERI1 Elena Savva Gene: eri1 has been classified as Red List (Low Evidence).
Skeletal Dysplasia_Fetal v0.204 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Skeletal Dysplasia_Fetal v0.204 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.204 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Skeletal Dysplasia_Fetal v0.204 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.203 ERI1 Elena Savva Marked gene: ERI1 as ready
Skeletal Dysplasia_Fetal v0.203 ERI1 Elena Savva Gene: eri1 has been classified as Red List (Low Evidence).
Mendeliome v1.956 RAB34 Sarah Pantaleo gene: RAB34 was added
gene: RAB34 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to PMID: 37384395
Phenotypes for gene: RAB34 were set to Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies
Penetrance for gene: RAB34 were set to Complete
Review for gene: RAB34 was set to GREEN
Added comment: Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogenous disorders characterised by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in >20 genes encoding ciliary proteins have been found to cause OFDS.

Identified by WES biallelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families (aided by GeneMatcher).

Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects.

RAB34 encodes a member of the Lab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Protein products of pathogenic variants clustered near the RAB34 C-terminus exhibit a strong loss of function.

Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, brain malformations), resulting in medical termination for three probands.

In the fourth, the only one alive at birth, proband born at 39+5 weeks, normal growth parameters after pregnancy with polyhydramnios, corpus callosum agenesis and polydactyly. Respiratory distress at birth.

All four probands presented typical features of ciliopathy disorders, overlapping with oral, facial and digital abnormalities.

All with homozygous missense variants. All absent in gnomAD (in homozygous state). Sanger sequencing confirmed mode of inheritance.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5251 ERI1 Elena Savva gene: ERI1 was added
gene: ERI1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 37352860
Phenotypes for gene: ERI1 were set to Intellectual disability (MONDO#0001071), ERI1-related
Review for gene: ERI1 was set to GREEN
Added comment: PMID: 37352860 - 8 individuals from 7 unrelated families
- Patients with biallelic missense show a MORE severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly
- Patients with biallelic null/whole gene deletion had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly
- Patient chet for a missense and PTC variant has a blended phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, mild ID and failure to thrive

- Missense variants were functionally shown to not be able to rescue 5.8S rRNA processing in KO HeLa cells
- K/O mice had neonatal lethality with growth defects, brachydactyly. Skeletal-specific K/O had mild platyspondyly, had more in keeping with patients with null variants than missense

More severe phenotype hypothesised due to "exonuclease-dead proteins may compete for the target RNA molecules with other exonucleases that have functional redundancy
with ERI1, staying bound to those RNA molecules"
Sources: Literature
Skeletal Dysplasia_Fetal v0.203 ERI1 Elena Savva gene: ERI1 was added
gene: ERI1 was added to Skeletal Dysplasia_Fetal. Sources: Literature
Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 37352860
Phenotypes for gene: ERI1 were set to Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related
Review for gene: ERI1 was set to GREEN
Added comment: PMID: 37352860 - 8 individuals from 7 unrelated families
- Patients with biallelic missense show a MORE severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly
- Patients with biallelic null/whole gene deletion had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly
- Patient chet for a missense and PTC variant has a blended phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, mild ID and failure to thrive

- Missense variants were functionally shown to not be able to rescue 5.8S rRNA processing in KO HeLa cells
- K/O mice had neonatal lethality with growth defects, brachydactyly. Skeletal-specific K/O had mild platyspondyly, had more in keeping with patients with null variants than missense

More severe phenotype hypothesised due to "exonuclease-dead proteins may compete for the target RNA molecules with other exonucleases that have functional redundancy
with ERI1, staying bound to those RNA molecules"
Sources: Literature
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.10 ERI1 Elena Savva Marked gene: ERI1 as ready
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.10 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.10 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.10 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Callosome v0.495 RAB34 Sarah Pantaleo gene: RAB34 was added
gene: RAB34 was added to Callosome. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to PMID: 37384395
Phenotypes for gene: RAB34 were set to Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies
Penetrance for gene: RAB34 were set to Complete
Review for gene: RAB34 was set to GREEN
Added comment: Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogenous disorders characterised by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in >20 genes encoding ciliary proteins have been found to cause OFDS.

Identified by WES biallelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families (aided by GeneMatcher).

Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects.

RAB34 encodes a member of the Lab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Protein products of pathogenic variants clustered near the RAB34 C-terminus exhibit a strong loss of function.

Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, brain malformations), resulting in medical termination for three probands.

In the fourth, the only one alive at birth, proband born at 39+5 weeks, normal growth parameters after pregnancy with polyhydramnios, corpus callosum agenesis and polydactyly. Respiratory distress at birth.

All four probands presented typical features of ciliopathy disorders, overlapping with oral, facial and digital abnormalities.

All with homozygous missense variants. All absent in gnomAD (in homozygous state). Sanger sequencing confirmed mode of inheritance.
Sources: Literature
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.9 ERI1 Elena Savva gene: ERI1 was added
gene: ERI1 was added to Multiple epiphyseal dysplasia and pseudoachondroplasia. Sources: Literature
Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 37352860
Review for gene: ERI1 was set to GREEN
Added comment: PMID: 37352860 - 8 individuals from 7 unrelated families
- Patients with biallelic missense show a MORE severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly
- Patients with biallelic null/whole gene deletion had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly
- Patient chet for a missense and PTC variant has a blended phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, mild ID and failure to thrive

- Missense variants were functionally shown to not be able to rescue 5.8S rRNA processing in KO HeLa cells
- K/O mice had neonatal lethality with growth defects, brachydactyly. Skeletal-specific K/O had mild platyspondyly, had more in keeping with patients with null variants than missense

More severe phenotype hypothesised due to "exonuclease-dead proteins may compete for the target RNA molecules with other exonucleases that have functional redundancy
with ERI1, staying bound to those RNA molecules"
Sources: Literature
Skeletal dysplasia v0.237 ERI1 Elena Savva Phenotypes for gene: ERI1 were changed from Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related, Intellectual disability (MONDO#0001071), ERI1-related to Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related
Inflammatory bowel disease v0.100 DKC1 Krithika Murali reviewed gene: DKC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32554502; Phenotypes: DKC1-related disorder - MONDO: 0100152; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting disorders v0.196 RAB34 Sarah Pantaleo gene: RAB34 was added
gene: RAB34 was added to Clefting disorders. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to PMID: 37384395
Phenotypes for gene: RAB34 were set to Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies
Penetrance for gene: RAB34 were set to Complete
Review for gene: RAB34 was set to GREEN
Added comment: Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogenous disorders characterised by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in >20 genes encoding ciliary proteins have been found to cause OFDS.

Identified by WES biallelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families (aided by GeneMatcher).

Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects.

RAB34 encodes a member of the Lab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Protein products of pathogenic variants clustered near the RAB34 C-terminus exhibit a strong loss of function.

Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, brain malformations), resulting in medical termination for three probands.

In the fourth, the only one alive at birth, proband born at 39+5 weeks, normal growth parameters after pregnancy with polyhydramnios, corpus callosum agenesis and polydactyly. Respiratory distress at birth.

All four probands presented typical features of ciliopathy disorders, overlapping with oral, facial and digital abnormalities.

All with homozygous missense variants. All absent in gnomAD (in homozygous state). Sanger sequencing confirmed mode of inheritance.
Sources: Literature
Genetic Epilepsy v0.1865 RPH3A Lucy Spencer gene: RPH3A was added
gene: RPH3A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RPH3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPH3A were set to 37403762; 29441694
Phenotypes for gene: RPH3A were set to Neurodevelopmental disorder (MONDO#0700092), RPH3A-related
Review for gene: RPH3A was set to GREEN
Added comment: PMID: 37403762- 6 patients with RPH3A variant. All 6 have ID, 4 have epilepsy, 2 with obesity, 1 with dysmorphic features. All 6 have missense variants, 3 shown to be de novo, the other 3 parents were not available for testing. I patient also had language and motor impairment, breathing issues and mixed hypo/hypertonia- he also had variants in CUL4B, PRKAG2, SCN4A, none of these genes cause seizures (which he had).

Patch clamp studies on 2 of the missense showed they increased either the number of NMDA receptors on neuron membrane surface or increased their conductance. Study suggests that the variants interrupt the normal role of RPH3A activity at the synaptic NMDAR complex which is needed for the induction of synaptic plasticity and NMDAR-dependant behaviours

Also previously 1 biallelic patient was reported, PMID: 29441694- 1 girl with learning disabilities, tremors, ataxia, hyperglycemia and muscle fatigability. Chet for 2 RPH3A missense. Functional analysis showed strong and marginal impairment of protein binding for each variant.
Sources: Literature
Mendeliome v1.956 DRG1 Dean Phelan gene: DRG1 was added
gene: DRG1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRG1 were set to PMID: 37179472
Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related
Review for gene: DRG1 was set to GREEN
Added comment: PMID: 37179472
- Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5250 RPH3A Lucy Spencer gene: RPH3A was added
gene: RPH3A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RPH3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPH3A were set to 37403762; 29441694
Phenotypes for gene: RPH3A were set to Neurodevelopmental disorder (MONDO#0700092), RPH3A-related
Review for gene: RPH3A was set to GREEN
Added comment: PMID: 37403762- 6 patients with RPH3A variant. All 6 have ID, 4 have epilepsy, 2 with obesity, 1 with dysmorphic features. All 6 have missense variants, 3 shown to be de novo, the other 3 parents were not available for testing. I patient also had language and motor impairment, breathing issues and mixed hypo/hypertonia- he also had variants in CUL4B, PRKAG2, SCN4A, none of these genes cause seizures (which he had).

Patch clamp studies on 2 of the missense showed they increased either the number of NMDA receptors on neuron membrane surface or increased their conductance. Study suggests that the variants interrupt the normal role of RPH3A activity at the synaptic NMDAR complex which is needed for the induction of synaptic plasticity and NMDAR-dependant behaviours

Also previously 1 biallelic patient was reported, PMID: 29441694- 1 girl with learning disabilities, tremors, ataxia, hyperglycemia and muscle fatigability. Chet for 2 RPH3A missense. Functional analysis showed strong and marginal impairment of protein binding for each variant.
Sources: Literature
Fetal anomalies v1.114 RAB34 Sarah Pantaleo gene: RAB34 was added
gene: RAB34 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to PMID: 37384395
Phenotypes for gene: RAB34 were set to Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies
Penetrance for gene: RAB34 were set to Complete
Review for gene: RAB34 was set to GREEN
Added comment: Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogenous disorders characterised by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in >20 genes encoding ciliary proteins have been found to cause OFDS.

Identified by WES biallelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families (aided by GeneMatcher).

Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects.

RAB34 encodes a member of the Lab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Protein products of pathogenic variants clustered near the RAB34 C-terminus exhibit a strong loss of function.

Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, brain malformations), resulting in medical termination for three probands.

In the fourth, the only one alive at birth, proband born at 39+5 weeks, normal growth parameters after pregnancy with polyhydramnios, corpus callosum agenesis and polydactyly. Respiratory distress at birth.

All four probands presented typical features of ciliopathy disorders, overlapping with oral, facial and digital abnormalities.

All with homozygous missense variants. All absent in gnomAD (in homozygous state). Sanger sequencing confirmed mode of inheritance.
Sources: Literature
Mendeliome v1.956 RPH3A Lucy Spencer gene: RPH3A was added
gene: RPH3A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPH3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPH3A were set to 37403762; 29441694
Phenotypes for gene: RPH3A were set to Neurodevelopmental disorder (MONDO#0700092), RPH3A-related
Review for gene: RPH3A was set to GREEN
Added comment: PMID: 37403762- 6 patients with RPH3A variant. All 6 have ID, 4 have epilepsy, 2 with obesity, 1 with dysmorphic features. All 6 have missense variants, 3 shown to be de novo, the other 3 parents were not available for testing. I patient also had language and motor impairment, breathing issues and mixed hypo/hypertonia- he also had variants in CUL4B, PRKAG2, SCN4A, none of these genes cause seizures (which he had).

Patch clamp studies on 2 of the missense showed they increased either the number of NMDA receptors on neuron membrane surface or increased their conductance. Study suggests that the variants interrupt the normal role of RPH3A activity at the synaptic NMDAR complex which is needed for the induction of synaptic plasticity and NMDAR-dependant behaviours

Previously this gene was reported in PMID: 29441694- 1 girl with learning disabilities, tremors, ataxia, hyperglycemia and muscle fatigability. Chet for 2 RPH3A missense. Functional analysis showed strong and marginal impairment of protein binding for each variant. this is the only biallelic report currently.
Sources: Literature
Mendeliome v1.956 MIR204 Chern Lim gene: MIR204 was added
gene: MIR204 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MIR204 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MIR204 were set to 26056285; 37321975
Phenotypes for gene: MIR204 were set to Retinal dystrophy and iris coloboma with or without cataract (MIM#616722)
Mode of pathogenicity for gene: MIR204 was set to Other
Review for gene: MIR204 was set to GREEN
gene: MIR204 was marked as current diagnostic
Added comment: PMID: 26056285
- Bilateral coloboma and rod-cone dystrophy with or without cataract in nine individuals of a five-generation family.
- Heterozygous n.37C>T segregates with the disease in all affected individuals.
- Functional analysis including transcriptome analysis showed this variant resulted in significant alterations of miR-204 targeting capabilities. In vivo injection, in medaka fish (Oryzias latipes), of the mutated miR-204 caused a phenotype consistent with that observed in the family.
- Authors suggested gain of function is the likely disease mechanism.

PMID: 37321975
- Four members of a three-generation family with early-onset chorioretinal dystrophy, heterozygous for n.37C>T.
- Additionally, four family members were shown to be affected by albinism resulting from biallelic pathogenic OCA2 variants.
- Haplotype analysis excluded relatedness with the family reported in PMID: 26056285.
- In silico analysis of the MIR204 n.37C>T variant reveals profound changes to its target mRNAs and suggests a gain-of-function mechanism of miR 204 variant.
Sources: Literature
Optic Atrophy v1.17 MIR204 Chern Lim gene: MIR204 was added
gene: MIR204 was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: MIR204 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MIR204 were set to 26056285; 37321975
Phenotypes for gene: MIR204 were set to Retinal dystrophy and iris coloboma with or without cataract (MIM#616722)
Mode of pathogenicity for gene: MIR204 was set to Other
Review for gene: MIR204 was set to GREEN
gene: MIR204 was marked as current diagnostic
Added comment: PMID: 26056285
- Bilateral coloboma and rod-cone dystrophy with or without cataract in nine individuals of a five-generation family.
- Heterozygous n.37C>T segregates with the disease in all affected individuals.
- Functional analysis including transcriptome analysis showed this variant resulted in significant alterations of miR-204 targeting capabilities. In vivo injection, in medaka fish (Oryzias latipes), of the mutated miR-204 caused a phenotype consistent with that observed in the family.
- Authors suggested gain of function is the likely disease mechanism.

PMID: 37321975
- Four members of a three-generation family with early-onset chorioretinal dystrophy, heterozygous for n.37C>T.
- Additionally, four family members were shown to be affected by albinism resulting from biallelic pathogenic OCA2 variants.
- Haplotype analysis excluded relatedness with the family reported in PMID: 26056285.
- In silico analysis of the MIR204 n.37C>T variant reveals profound changes to its target mRNAs and suggests a gain-of-function mechanism of miR 204 variant.
Sources: Literature
Skeletal dysplasia v0.236 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Skeletal dysplasia v0.236 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.235 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Skeletal dysplasia v0.235 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.234 ERI1 Elena Savva Marked gene: ERI1 as ready
Skeletal dysplasia v0.234 ERI1 Elena Savva Gene: eri1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.234 ERI1 Elena Savva gene: ERI1 was added
gene: ERI1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 37352860
Phenotypes for gene: ERI1 were set to Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related, Intellectual disability (MONDO#0001071), ERI1-related
Review for gene: ERI1 was set to GREEN
Added comment: PMID: 37352860 - 8 individuals from 7 unrelated families
- Patients with biallelic missense show a MORE severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly
- Patients with biallelic null/whole gene deletion had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly
- Patient chet for a missense and PTC variant has a blended phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, mild ID and failure to thrive

- Missense variants were functionally shown to not be able to rescue 5.8S rRNA processing in KO HeLa cells
- K/O mice had neonatal lethality with growth defects, brachydactyly. Skeletal-specific K/O had mild platyspondyly, had more in keeping with patients with null variants than missense

More severe phenotype hypothesised due to "exonuclease-dead proteins may compete for the target RNA molecules with other exonucleases that have functional redundancy
with ERI1, staying bound to those RNA molecules"
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5250 DRG1 Dean Phelan gene: DRG1 was added
gene: DRG1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRG1 were set to PMID: 37179472
Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related
Review for gene: DRG1 was set to GREEN
Added comment: PMID: 37179472
- Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function.
Sources: Literature
Cerebral vascular malformations v0.32 ANO1 Suliman Khan gene: ANO1 was added
gene: ANO1 was added to Cerebral vascular malformations. Sources: Literature
Mode of inheritance for gene: ANO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANO1 were set to PMID: 37253099
Phenotypes for gene: ANO1 were set to moyamoya; cerebral arteriopathy
Review for gene: ANO1 was set to GREEN
Added comment: PMID: 37253099: screening analysis of Moyamoya disease (MMD) cohort revealed 8 patients with variants in the ANO1 gene. Two families had the same rare variant p.Met658Val in ANO1 gene. The ANO1 rare variants were assessed using patch-clamp recordings, and the majority of variants, including ANO1 p.Met658Val, displayed increased sensitivity to intracellular Ca2+. Patients harboring these gain-of-function ANO1 variants had classic features of MMD, but also had aneurysm, stenosis, and/or occlusion in the posterior circulation.
Sources: Literature
Hereditary Neuropathy - complex v0.166 ERCC6 Sangavi Sivagnanasundram reviewed gene: ERCC6: Rating: RED; Mode of pathogenicity: None; Publications: 20301516; Phenotypes: Cockayne syndrome, type B MIM#133540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neuromuscular Superpanel v1.28 Zornitza Stark Panel types changed to Superpanel; Victorian Clinical Genetics Services; Royal Melbourne Hospital
Hereditary Neuropathy - complex v0.166 GALC Sangavi Sivagnanasundram reviewed gene: GALC: Rating: AMBER; Mode of pathogenicity: None; Publications: 20301416, 21070211; Phenotypes: Krabbe Disease MIM#245200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.166 FAM126A Sangavi Sivagnanasundram reviewed gene: FAM126A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 5 MIM#610532; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.166 ZFYVE26 Sangavi Sivagnanasundram reviewed gene: ZFYVE26: Rating: GREEN; Mode of pathogenicity: None; Publications: 17661097, 19438933; Phenotypes: Spastic paraplegia 15 MIM#270700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuria v0.220 CD2AP Bryony Thompson Phenotypes for gene: CD2AP were changed from focal segmental glomerulosclerosis 3, susceptibility to MONDO:0011917 to focal segmental glomerulosclerosis 3, susceptibility to MONDO:0011917
Proteinuria v0.219 CD2AP Bryony Thompson Phenotypes for gene: CD2AP were changed from Glomerulosclerosis, focal segmental, 3, OMIM #607832 to focal segmental glomerulosclerosis 3, susceptibility to MONDO:0011917
Proteinuria v0.218 CD2AP Bryony Thompson Publications for gene: CD2AP were set to 30612599; 17713465
Proteinuria v0.217 CD2AP Bryony Thompson Mode of inheritance for gene: CD2AP was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Proteinuria v0.216 CD2AP Bryony Thompson Classified gene: CD2AP as Green List (high evidence)
Proteinuria v0.216 CD2AP Bryony Thompson Added comment: Comment on list classification: Comment on list classification: Definitive gene-disease assessment by ClinGen Glomerulopathy GCEP - classified 13/12/2021
Proteinuria v0.216 CD2AP Bryony Thompson Gene: cd2ap has been classified as Green List (High Evidence).
Mendeliome v1.956 CD2AP Bryony Thompson Phenotypes for gene: CD2AP were changed from Glomerulosclerosis, focal segmental, 3, OMIM #607832 to focal segmental glomerulosclerosis 3, susceptibility to MONDO:0011917
Mendeliome v1.955 CD2AP Bryony Thompson Publications for gene: CD2AP were set to 30612599; 17713465; 10997929; 12764198; 15951437
Mendeliome v1.954 CD2AP Bryony Thompson Publications for gene: CD2AP were set to 30612599; 17713465
Mendeliome v1.953 CD2AP Bryony Thompson Mode of inheritance for gene: CD2AP was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.952 CD2AP Bryony Thompson Classified gene: CD2AP as Green List (high evidence)
Mendeliome v1.952 CD2AP Bryony Thompson Added comment: Comment on list classification: Definitive gene-disease assessment by ClinGen Glomerulopathy GCEP - classified 13/12/2021
Mendeliome v1.952 CD2AP Bryony Thompson Gene: cd2ap has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.175 CBLB Zornitza Stark Phenotypes for gene: CBLB were changed from Autoimmune disease, MONDO:0007179 to Autoimmune disease, multisystem, infantile-onset, 3, MIM# 620430
Mendeliome v1.951 CBLB Zornitza Stark Phenotypes for gene: CBLB were changed from Autoimmune disease, MONDO:0007179 to Autoimmune disease, multisystem, infantile-onset, 3, MIM# 620430
Syndromic Retinopathy v0.201 INTS11 Zornitza Stark Marked gene: INTS11 as ready
Syndromic Retinopathy v0.201 INTS11 Zornitza Stark Gene: ints11 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.201 INTS11 Zornitza Stark Classified gene: INTS11 as Green List (high evidence)
Syndromic Retinopathy v0.201 INTS11 Zornitza Stark Gene: ints11 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.200 INTS11 Zornitza Stark gene: INTS11 was added
gene: INTS11 was added to Syndromic Retinopathy. Sources: Expert Review
Mode of inheritance for gene: INTS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS11 were set to 37054711
Phenotypes for gene: INTS11 were set to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, MIM# 620428
Review for gene: INTS11 was set to GREEN
Added comment: PMID: 37054711 - 15 individuals from 10 unrelated families with bi-allelic variants in INTS11 with global developmental and language delay, intellectual disability, impaired motor development, and brain atrophy. Functional studies in Drosophila showed that dIntS11 (fly ortholog of INTS11) is essential and expressed in the central nervous systems in a subset of neurons and most glia in larval and adult stages.

Retinal dystrophy reported.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5250 INTS11 Zornitza Stark Phenotypes for gene: INTS11 were changed from intellectual disability, MONDO:0001071 to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, MIM# 620428
Mendeliome v1.950 INTS11 Zornitza Stark Phenotypes for gene: INTS11 were changed from intellectual disability, MONDO:0001071 to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, MIM# 620428
Intellectual disability syndromic and non-syndromic v0.5249 SRRM2 Zornitza Stark Publications for gene: SRRM2 were set to 33057194
Intellectual disability syndromic and non-syndromic v0.5248 SRRM2 Zornitza Stark Phenotypes for gene: SRRM2 were changed from neurodevelopmental disorder MONDO:0700092 SRRM2-related to Intellectual developmental disorder, autosomal dominant 72, MIM# 620439
Mendeliome v1.949 SRRM2 Zornitza Stark Phenotypes for gene: SRRM2 were changed from Neurodevelopmental disorder MONDO:0700092 SRRM2-related to Intellectual developmental disorder, autosomal dominant 72, MIM# 620439
Early-onset Parkinson disease v0.240 ATP7B Sangavi Sivagnanasundram reviewed gene: ATP7B: Rating: AMBER; Mode of pathogenicity: None; Publications: 31426520, 33972609, 36553628, 16737839; Phenotypes: Wilson disease (MONDO:0010200); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Dystonia - complex v0.224 NUP54 Zornitza Stark Phenotypes for gene: NUP54 were changed from Striatonigral degeneration, MONDO:0003122, NUP54-related; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia to Dystonia 37, early-onset, with striatal lesions, MIM# 620427; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia
Mendeliome v1.948 NUP54 Zornitza Stark Phenotypes for gene: NUP54 were changed from Striatonigral degeneration, MONDO:0003122, NUP54-related; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia to Dystonia 37, early-onset, with striatal lesions, MIM# 620427; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia
Genomic newborn screening: BabyScreen+ v0.2175 MT-RNR1 Zornitza Stark changed review comment from: The following variants have been associated with aminoglycoside-induced deafness:
m.1555A>G
m.1005T>C
m.1095T>C

Alerts can be placed in medical records to avoid aminoglycoside administration.
Sources: Expert Review; to: The following variants have been associated with aminoglycoside-induced deafness:
m.1555A>G and m.1494C>T

Alerts can be placed in medical records to avoid aminoglycoside administration.
Sources: Expert Review
Fetal anomalies v1.114 BRWD1 Zornitza Stark Phenotypes for gene: BRWD1 were changed from Situs inversus; primary ciliary dyskinesia like to Situs inversus; Ciliary dyskinesia, primary, 51, MIM# 620438
Mendeliome v1.947 BRWD1 Zornitza Stark Phenotypes for gene: BRWD1 were changed from Asthenoteratozoospermia, likely primary ciliary dyskinesia to Ciliary dyskinesia, primary, 51, MIM# 620438
Ciliary Dyskinesia v1.31 BRWD1 Zornitza Stark Phenotypes for gene: BRWD1 were changed from Primary ciliary dyskinesia, asthenoteratozoospermia to Ciliary dyskinesia, primary, 51, MIM# 620438
Ciliary Dyskinesia v1.30 BRWD1 Zornitza Stark edited their review of gene: BRWD1: Changed phenotypes: Ciliary dyskinesia, primary, 51, MIM# 620438
Epidermolysis bullosa v1.15 SPINK5 Bryony Thompson Marked gene: SPINK5 as ready
Epidermolysis bullosa v1.15 SPINK5 Bryony Thompson Gene: spink5 has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.15 SPINK5 Bryony Thompson Mode of pathogenicity for gene: SPINK5 was changed from Other to None
Epidermolysis bullosa v1.14 SPINK5 Bryony Thompson Classified gene: SPINK5 as Green List (high evidence)
Epidermolysis bullosa v1.14 SPINK5 Bryony Thompson Gene: spink5 has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.13 KRT6C Bryony Thompson Marked gene: KRT6C as ready
Epidermolysis bullosa v1.13 KRT6C Bryony Thompson Gene: krt6c has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.13 KRT6C Bryony Thompson Classified gene: KRT6C as Green List (high evidence)
Epidermolysis bullosa v1.13 KRT6C Bryony Thompson Gene: krt6c has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.12 KRT6B Bryony Thompson Marked gene: KRT6B as ready
Epidermolysis bullosa v1.12 KRT6B Bryony Thompson Gene: krt6b has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.12 KRT6B Bryony Thompson Classified gene: KRT6B as Green List (high evidence)
Epidermolysis bullosa v1.12 KRT6B Bryony Thompson Gene: krt6b has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.11 KRT6A Bryony Thompson Marked gene: KRT6A as ready
Epidermolysis bullosa v1.11 KRT6A Bryony Thompson Gene: krt6a has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.11 KRT6A Bryony Thompson Classified gene: KRT6A as Green List (high evidence)
Epidermolysis bullosa v1.11 KRT6A Bryony Thompson Gene: krt6a has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.10 KRT17 Bryony Thompson Marked gene: KRT17 as ready
Epidermolysis bullosa v1.10 KRT17 Bryony Thompson Gene: krt17 has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.10 KRT17 Bryony Thompson Classified gene: KRT17 as Green List (high evidence)
Epidermolysis bullosa v1.10 KRT17 Bryony Thompson Gene: krt17 has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.9 KRT17 Bryony Thompson Mode of pathogenicity for gene: KRT17 was changed from None to Other
Epidermolysis bullosa v1.8 KRT16 Bryony Thompson Marked gene: KRT16 as ready
Epidermolysis bullosa v1.8 KRT16 Bryony Thompson Gene: krt16 has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.8 KRT16 Bryony Thompson Classified gene: KRT16 as Green List (high evidence)
Epidermolysis bullosa v1.8 KRT16 Bryony Thompson Gene: krt16 has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.7 FLG2 Bryony Thompson Deleted their review
Epidermolysis bullosa v1.7 FLG2 Bryony Thompson commented on gene: FLG2
Epidermolysis bullosa v1.7 FLG2 Bryony Thompson Classified gene: FLG2 as Green List (high evidence)
Epidermolysis bullosa v1.7 FLG2 Bryony Thompson Gene: flg2 has been classified as Green List (High Evidence).
Epidermolysis bullosa v1.6 FLG2 Bryony Thompson Deleted their review
Cerebral Palsy v1.88 PMM2 Luisa Weiss gene: PMM2 was added
gene: PMM2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PMM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PMM2 were set to 34788679
Phenotypes for gene: PMM2 were set to Congenital disorder of glycosylation, type Ia MIM#212065
Review for gene: PMM2 was set to AMBER
Added comment: One patient in a large CP cohort study was found to have biallelic mutations ins PMM2, but usually PMM2-CDG presents as a progressive multisystem disease with dysmorphism.
Sources: Literature
Cerebral Palsy v1.88 PLP1 Luisa Weiss gene: PLP1 was added
gene: PLP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PLP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PLP1 were set to 33528536; 25280894; 34816117
Phenotypes for gene: PLP1 were set to Pelizaeus-Merzbacher disease MIM#312080; Spastic paraplegia 2, X-linked MIM#312920
Review for gene: PLP1 was set to GREEN
Added comment: Three large cohort studies with patients initially presenting as CP found three individuals with hemizygous mutations in PLP1. Note that individuals ins PMID 33528536 and 34816117 had different base pair exchanges at the same splice site location (NM_000533:c.191+1G>T and c.191+1G>A, respectively). The other mutation was a PLP1 gene duplication. One patient also had a affected brother.
Sources: Literature
Cerebral Palsy v1.88 PLA2G6 Luisa Weiss gene: PLA2G6 was added
gene: PLA2G6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PLA2G6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLA2G6 were set to 33528536; 34540776; 34788679
Phenotypes for gene: PLA2G6 were set to Infantile neuroaxonal dystrophy 1 MIM#256600; Neurodegeneration with brain iron accumulation 2B MIM#610217; Parkinson disease 14, autosomal recessive MIM#612953
Review for gene: PLA2G6 was set to GREEN
Added comment: Three different individuals from three large CP cohort studies presenting with biallelic PLA2G6 mutations.
Sources: Literature
Cerebral Palsy v1.88 PIGA Luisa Weiss gene: PIGA was added
gene: PIGA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PIGA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PIGA were set to 33528536; 24706016
Phenotypes for gene: PIGA were set to Multiple congenital anomalies-hypotonia-seizures syndrome 2 MIM#300868; Neurodevelopmental disorder with epilepsy and hemochromatosis MIM#301072; Paroxysmal nocturnal hemoglobinuria, somatic MIM#300818
Review for gene: PIGA was set to GREEN
Added comment: One case in a large CP cohort study with maternally inherited PIGA mutation predicted to be likely pathogenic.
In addition, Kato (PMID 24706016) reviewed 7 cases of boys with hemizygous PIGA mutations and encephalopathies, two of which had non-progressive hypotonic quadriplegia and one had spastic quadriplegia. They also showed intellectual disability and seizures. No CP diagnoses was given, but phenotypic overlap is present.
Sources: Literature
Cerebral Palsy v1.88 PDHX Luisa Weiss gene: PDHX was added
gene: PDHX was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PDHX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDHX were set to 33528536; 35076175; 34540776
Phenotypes for gene: PDHX were set to Lacticacidemia due to PDX1 deficiency MIM#245349
Review for gene: PDHX was set to GREEN
Added comment: Three individual patients from three large CP cohort studies with homozygous PDHX mutations. Note that in one case (PMID 35076175) the patient had both homozygous PDHX and homozygous ACADM mutations, but his phenotype was more consistent with PDHX mutations.
Sources: Literature
Cerebral Palsy v1.88 PDHA1 Luisa Weiss gene: PDHA1 was added
gene: PDHA1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PDHA1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: PDHA1 were set to 33528536; 10486093
Phenotypes for gene: PDHA1 were set to Pyruvate dehydrogenase E1-alpha deficiency MIM#312170
Review for gene: PDHA1 was set to GREEN
Added comment: 2 patients in 1 large CP cohort presented with heterozygous likely pathogenic missense mutations, one of them confirmed de novo.
In an older case report (PMID:10486093) two unrelated girls were presented with cerebral palsy which were found to harbor heterozygous PDHA mutations. In one case, parental DNA wasn't analyzed, in the other case the mutation wasn't found in the healthy mother and the healthy brother of the patient. Both girls showed skewed X-Inactivation.
Note that in X-linked PDH deficiency it has been shown that a high proportion of heterozygous females manifest severe symptoms.
Sources: Literature
Cerebral Palsy v1.88 PANK2 Luisa Weiss reviewed gene: PANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33098801, 34114234, 25131622; Phenotypes: HARP syndrome MIM#607236, Neurodegeneration with brain iron accumulation MIM#234200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.88 PAK3 Luisa Weiss reviewed gene: PAK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31444167, 30542205, 25666757; Phenotypes: Intellectual developmental disorder, X-linked MIM#300558; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.88 PAFAH1B1 Luisa Weiss gene: PAFAH1B1 was added
gene: PAFAH1B1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PAFAH1B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAFAH1B1 were set to 19667223
Phenotypes for gene: PAFAH1B1 were set to Lissencephaly MIM#607432; Subcortical laminar heterotopia MIM#607432
Review for gene: PAFAH1B1 was set to GREEN
Added comment: Saillour reviewed 63 patients with posteriorly predominant lissencephaly, 40 of which were proven to have a LIS1 mutation. None of them were officially diagnosed with cerebral palsy, however, 24 of those 40 patients presented with "severe motor impairment including axial hypotonia and spastic quadriparesis". A high percentage of patients also showed severe developmental delay and epilepsy.
Sources: Literature
Cerebral Palsy v1.88 NFIX Luisa Weiss gene: NFIX was added
gene: NFIX was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NFIX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFIX were set to 34788679
Phenotypes for gene: NFIX were set to Malan syndrome MIM#614753; Marshall-Smith syndrome MIM#602535
Review for gene: NFIX was set to AMBER
Added comment: Two patients in a large CP cohort study, one with a nonsense mutation without information on inheritance and one with a de novo missense mutation predicted to be likely pathogenic. Normally, NFIX mutation cause accelerated bone maturation with overgrwowth, dysmorphism and mental retardation, so there is a low possibility for phenotypic overlap.
Sources: Literature
Cerebral Palsy v1.88 NAA10 Luisa Weiss gene: NAA10 was added
gene: NAA10 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NAA10 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: NAA10 were set to 33528536; 30542205
Phenotypes for gene: NAA10 were set to Microphthalmia, syndromic MIM#309800; Ogden syndrome MIM#300855
Review for gene: NAA10 was set to GREEN
Added comment: Four individual cases in two large CP cohort studies. Note that in one publication (33528536) 2/3 mutations occurred de novo.
Sources: Literature
Cerebral Palsy v1.88 MT-TL1 Luisa Weiss gene: MT-TL1 was added
gene: MT-TL1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene gene: MT-TL1 was set to MITOCHONDRIAL
Publications for gene: MT-TL1 were set to 34531397; 34077496; 25280894
Phenotypes for gene: MT-TL1 were set to MYOCLONIC EPILEPSY ASSOCIATED WITH RAGGED-RED FIBERS MERRF MIM#545000; CYCLIC VOMITING SYNDROME WITH NEUROMUSCULAR DISEASE, INCLUDED CYCLIC VOMITING SYNDROME-PLUS, INCLUDED CVS-PLUS, INCLUDED MIM#500007; MITOCHONDRIAL MYOPATHY, ENCEPHALOPATHY, LACTIC ACIDOSIS, AND STROKE-LIKE EPISODES MELAS MIM#540000; DIABETES AND DEAFNESS, MATERNALLY INHERITED MIDD MIM#520000
Review for gene: MT-TL1 was set to GREEN
Added comment: Three individual cases in three different large CP cohort publications. In one case, heteroplasmy was 8% in another it was 58% with a low level detectable also in the mother. The third does not state the heteroplasmy level. Note very high intra- and interfamilial variability, partly due to heteroplasmy level in different tissues.
Sources: Literature
Mendeliome v1.946 UBE3B Achchuthan Shanmugasundram reviewed gene: UBE3B: Rating: AMBER; Mode of pathogenicity: None; Publications: 23200864, 23687348, 37010288; Phenotypes: Kaufman oculocerebrofacial syndrome, OMIM:244450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.946 SMARCB1 Achchuthan Shanmugasundram reviewed gene: SMARCB1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25168959, 37010288; Phenotypes: Coffin-Siris syndrome 3, OMIM:614608; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.946 NOTCH2 Achchuthan Shanmugasundram reviewed gene: NOTCH2: Rating: AMBER; Mode of pathogenicity: None; Publications: 9188663, 30329210, 37010288; Phenotypes: Hajdu-Cheney syndrome, OMIM:102500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.946 AUTS2 Achchuthan Shanmugasundram reviewed gene: AUTS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31788251, 37010288; Phenotypes: Intellectual developmental disorder, autosomal dominant 26, OMIM:615834; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.946 ARID1A Achchuthan Shanmugasundram reviewed gene: ARID1A: Rating: AMBER; Mode of pathogenicity: None; Publications: 25168959, 37010288; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Epidermolysis bullosa v1.5 SPINK5 Sangavi Sivagnanasundram gene: SPINK5 was added
gene: SPINK5 was added to Epidermolysis bullosa. Sources: Other
Mode of inheritance for gene: SPINK5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPINK5 were set to 19683336
Phenotypes for gene: SPINK5 were set to Netherton syndrome (MIM#256500)
Mode of pathogenicity for gene: SPINK5 was set to Other
Review for gene: SPINK5 was set to GREEN
Added comment: Characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels.
Typically caused by either homozygous or compound heterozygous mutations.

PMID: 19683336
9 unrelated children with Comel-Netherton syndrome with homozygous mutations in SPINK5.
Sources: Other
Epidermolysis bullosa v1.5 KRT17 Sangavi Sivagnanasundram gene: KRT17 was added
gene: KRT17 was added to Epidermolysis bullosa. Sources: Other
Mode of inheritance for gene: KRT17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRT17 were set to 11886499; 21326300
Phenotypes for gene: KRT17 were set to Pachyonychia congenita 2 (MIM#167210)
Review for gene: KRT17 was set to GREEN
Added comment: Also reported as Jackson-Lawler type syndrome

PMID: 11886499
4 unrelated individuals with pachyonychia congenita like phenotype

PMID: 21326300
Heterozygous pathogenic mutations have a dominant-negative effect on the KRT17 protein
Sources: Other
Epidermolysis bullosa v1.5 KRT16 Sangavi Sivagnanasundram gene: KRT16 was added
gene: KRT16 was added to Epidermolysis bullosa. Sources: Other
Mode of inheritance for gene: KRT16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRT16 were set to 16250206
Phenotypes for gene: KRT16 were set to Pachyonychia congenita 1 (MIM#167200)
Mode of pathogenicity for gene: KRT16 was set to Other
Review for gene: KRT16 was set to GREEN
Added comment: PMID: 16250206
Typically identified by nail bed, palmoplantar epidermis (widespread), epidermal appendages, oral mucosa and wound healing.
>5 unrelated families with a consistent phenotype of PC and a heterozygous missense variant in KRT16.
Sources: Other
Epidermolysis bullosa v1.5 KRT6C Sangavi Sivagnanasundram gene: KRT6C was added
gene: KRT6C was added to Epidermolysis bullosa. Sources: Other
Mode of inheritance for gene: KRT6C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRT6C were set to 31823354; 23662636
Phenotypes for gene: KRT6C were set to Palmoplantar keratoderma, nonepidermolytic, focal or diffuse (MIM#615735)
Mode of pathogenicity for gene: KRT6C was set to Other
Review for gene: KRT6C was set to GREEN
Added comment: Phenotype overlap with Pachyonychia congenita (PC)

PMID: 31823354
Approx 23 unrelated families with mutation in KRT6C with phenotypes consistent with pachyonchia congenita

PMID: 23662636
In vitro assay in HaCaT cells showed the overexpression of mutant keratin 6c showed a collapse of the keratin filament network suggestive of dominant negative effect pathogenicity.
Sources: Other
Epidermolysis bullosa v1.5 KRT6B Sangavi Sivagnanasundram gene: KRT6B was added
gene: KRT6B was added to Epidermolysis bullosa. Sources: Other
Mode of inheritance for gene: KRT6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRT6B were set to 24611874; 21326300
Phenotypes for gene: KRT6B were set to Pachyonychia congenita 4 MIM#615728
Mode of pathogenicity for gene: KRT6B was set to Other
Review for gene: KRT6B was set to GREEN
Added comment: Previously known as Jadassohn-Lewandowsky PC type 1 and Jackson-Lawler PC type 2
Mutants are found to have a dominant-negative most of pathogenicity.

PMID: 24611874
Multiple families with either plantar keratoderma or palmopantar keratoderma phenotypes with a mutation in KRT6B

PMID: 21326300
The most common reported mutation K6b p.Glu472Lys in families with KRT6B-related Pachyonychia congenita
Sources: Other
Epidermolysis bullosa v1.5 KRT6A Sangavi Sivagnanasundram gene: KRT6A was added
gene: KRT6A was added to Epidermolysis bullosa. Sources: Other
Mode of inheritance for gene: KRT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRT6A were set to 32017015; 21326300
Phenotypes for gene: KRT6A were set to Pachyonychia congenita 3 MIM#615726
Mode of pathogenicity for gene: KRT6A was set to Other
Review for gene: KRT6A was set to GREEN
Added comment: Well established gene-disease association.

Multiple families reported with hyperkeratotic disorders with skin fragility like symptoms.
p.Asn172del is the most common mutation identified in families with Pachyonychia congenita
Sources: Other
Mendeliome v1.946 ZC4H2 Achchuthan Shanmugasundram changed review comment from: There are ten unrelated patients reported with cleft palate. Hence, this gene should be added with green rating to 'clefting disorders' panel.

PMID:31206972 - Of 42 families identified with variants in de novo and inherited heterozygous variants in ZC4H2 gene, eight patients had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with monoallelic sequence variants, three patients had cleft palate.

Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM.; to: There are ten unrelated patients reported with cleft palate. Hence, this gene should be added with green rating to 'clefting disorders' panel.

PMID:31206972 - Of 42 families identified with de novo and inherited variants in ZC4H2 gene, eight patients had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with sequence variants, three patients had cleft palate.

Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM.
Mendeliome v1.946 ZC4H2 Achchuthan Shanmugasundram edited their review of gene: ZC4H2: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.946 ZC4H2 Achchuthan Shanmugasundram edited their review of gene: ZC4H2: Changed publications: 31206972, 37010288; Changed phenotypes: Wieacker-Wolff syndrome, female-restricted, OMIM:301041
Mendeliome v1.946 ZC4H2 Achchuthan Shanmugasundram reviewed gene: ZC4H2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mitochondrial disease v0.877 GCSH Zornitza Stark Marked gene: GCSH as ready
Mitochondrial disease v0.877 GCSH Zornitza Stark Gene: gcsh has been classified as Green List (High Evidence).
Mitochondrial disease v0.877 GCSH Zornitza Stark Classified gene: GCSH as Green List (high evidence)
Mitochondrial disease v0.877 GCSH Zornitza Stark Gene: gcsh has been classified as Green List (High Evidence).
Mitochondrial disease v0.876 GCSH Zornitza Stark gene: GCSH was added
gene: GCSH was added to Mitochondrial disease. Sources: Expert Review
Mode of inheritance for gene: GCSH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCSH were set to 33890291; 36190515
Phenotypes for gene: GCSH were set to Multiple mitochondrial dysfunctions syndrome 7, MIM# 620423
Review for gene: GCSH was set to GREEN
Added comment: 7 unrelated families reported. Phenotype ranges from neonatal fatal glycine encephalopathy to an attenuated phenotype of developmental delay, behavioral problems, limited epilepsy and variable movement problems.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5247 GCSH Zornitza Stark Phenotypes for gene: GCSH were changed from Glycine encephalopathy MIM#605899; neurodevelopmental disorder MONDO#0700092, GCHS-related to Multiple mitochondrial dysfunctions syndrome 7, MIM# 620423
Callosome v0.495 GCSH Zornitza Stark Phenotypes for gene: GCSH were changed from Glycine encephalopathy, MIM#605899 to Multiple mitochondrial dysfunctions syndrome 7, MIM# 620423
Genetic Epilepsy v0.1865 GCSH Zornitza Stark Phenotypes for gene: GCSH were changed from Glycine encephalopathy MIM#605899; neurodevelopmental disorder MONDO#0700092, GCHS-related to Multiple mitochondrial dysfunctions syndrome 7, MIM# 620423
Mendeliome v1.946 GCSH Zornitza Stark Phenotypes for gene: GCSH were changed from Glycine encephalopathy MIM#605899; neurodevelopmental disorder MONDO#0700092, GCHS-related to Multiple mitochondrial dysfunctions syndrome 7, MIM# 620423
Motor Neurone Disease v0.189 SCA2 Bryony Thompson Marked STR: SCA2 as ready
Motor Neurone Disease v0.189 SCA2 Bryony Thompson Str: sca2 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.189 SCA2 Bryony Thompson Classified STR: SCA2 as Green List (high evidence)
Motor Neurone Disease v0.189 SCA2 Bryony Thompson Str: sca2 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.188 SCA2 Bryony Thompson STR: SCA2 was added
STR: SCA2 was added to Motor Neurone Disease. Sources: Literature
Mode of inheritance for STR: SCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA2 were set to 20301452
Phenotypes for STR: SCA2 were set to Spinocerebellar ataxia 2 MIM#183090
Review for STR: SCA2 was set to GREEN
STR: SCA2 was marked as clinically relevant
Added comment: NM_002973​.3:c.496_498CAG[X]
Toxic protein aggregation is mechanism of disease
Benign: ≤31 repeats (homozygous 31/31 repeats reported for recessive SCA2)
Uncertain: 32 repeats
ALS risk allele: 30-32 repeats
Reduced penetrance: 33-34 repeats, may not develop symptoms or only very late in life
Full penetrance: ≥35 repeats
Interruption of a CAG expanded allele by a CAA repeat does not mitigate the pathogenicity of the repeat size, but may enhance the meiotic stability of the repeat
Sources: Literature
Motor Neurone Disease v0.187 LGALSL Bryony Thompson Marked gene: LGALSL as ready
Motor Neurone Disease v0.187 LGALSL Bryony Thompson Gene: lgalsl has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.187 LGALSL Bryony Thompson Classified gene: LGALSL as Amber List (moderate evidence)
Motor Neurone Disease v0.187 LGALSL Bryony Thompson Gene: lgalsl has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.186 LGALSL Bryony Thompson gene: LGALSL was added
gene: LGALSL was added to Motor Neurone Disease. Sources: ClinGen
Mode of inheritance for gene: LGALSL was set to Unknown
Publications for gene: LGALSL were set to 30940688
Phenotypes for gene: LGALSL were set to amyotrophic lateral sclerosis MONDO:0004976
Review for gene: LGALSL was set to AMBER
Added comment: Limited gene-disease validity assessment by ClinGen ALS spectrum disorder GCEP - 14/02/2023. Significant enrichment in a cohort of 3,239 ALS cases compared to 11,808 controls - OR = 14.63; P = 2.29e-6.
Sources: ClinGen
Motor Neurone Disease v0.185 HNRNPA2B1 Bryony Thompson Marked gene: HNRNPA2B1 as ready
Motor Neurone Disease v0.185 HNRNPA2B1 Bryony Thompson Gene: hnrnpa2b1 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.185 HNRNPA2B1 Bryony Thompson gene: HNRNPA2B1 was added
gene: HNRNPA2B1 was added to Motor Neurone Disease. Sources: ClinGen
Mode of inheritance for gene: HNRNPA2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPA2B1 were set to 25299611
Phenotypes for gene: HNRNPA2B1 were set to amyotrophic lateral sclerosis MONDO:0004976
Review for gene: HNRNPA2B1 was set to RED
Added comment: Limited gene-disease validity assessment by ALS spectrum disorder GCEP - 15/12/2021. Only one variant in a single ALS proband scored.
Sources: ClinGen
Motor Neurone Disease v0.184 GRN Bryony Thompson Marked gene: GRN as ready
Motor Neurone Disease v0.184 GRN Bryony Thompson Gene: grn has been classified as Green List (High Evidence).
Motor Neurone Disease v0.184 GRN Bryony Thompson Classified gene: GRN as Green List (high evidence)
Motor Neurone Disease v0.184 GRN Bryony Thompson Gene: grn has been classified as Green List (High Evidence).
Motor Neurone Disease v0.183 GRN Bryony Thompson gene: GRN was added
gene: GRN was added to Motor Neurone Disease. Sources: ClinGen
Mode of inheritance for gene: GRN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRN were set to 18184915; 23596077
Phenotypes for gene: GRN were set to frontotemporal dementia and/or amyotrophic lateral sclerosis MONDO:0030923
Review for gene: GRN was set to GREEN
gene: GRN was marked as current diagnostic
Added comment: Well-established FTD gene. ALS has been reported in association with some GRN variants, but appears to be a rare occurrence.
Sources: ClinGen
Motor Neurone Disease v0.182 GLT8D1 Bryony Thompson Marked gene: GLT8D1 as ready
Motor Neurone Disease v0.182 GLT8D1 Bryony Thompson Gene: glt8d1 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.182 GLT8D1 Bryony Thompson Classified gene: GLT8D1 as Amber List (moderate evidence)
Motor Neurone Disease v0.182 GLT8D1 Bryony Thompson Gene: glt8d1 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.181 FIG4 Bryony Thompson Marked gene: FIG4 as ready
Motor Neurone Disease v0.181 FIG4 Bryony Thompson Gene: fig4 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.181 FIG4 Bryony Thompson Phenotypes for gene: FIG4 were changed from to Amyotrophic Lateral Sclerosis Type 11 (MONDO: 0012945; MIM#612577)
Motor Neurone Disease v0.180 FIG4 Bryony Thompson Mode of inheritance for gene: FIG4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.179 FIG4 Bryony Thompson Classified gene: FIG4 as Amber List (moderate evidence)
Motor Neurone Disease v0.179 FIG4 Bryony Thompson Added comment: Comment on list classification: Limited gene-disease validity assessment by ClinGen ALS spectrum disorders GCEP - 09/08/2022
Motor Neurone Disease v0.179 FIG4 Bryony Thompson Gene: fig4 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.178 EWSR1 Bryony Thompson Classified gene: EWSR1 as Red List (low evidence)
Motor Neurone Disease v0.178 EWSR1 Bryony Thompson Added comment: Comment on list classification: Disputed gene-disease validity assessment by ClinGen ALS spectrum disorders GCEP - 11/10/2022
Motor Neurone Disease v0.178 EWSR1 Bryony Thompson Gene: ewsr1 has been classified as Red List (Low Evidence).
Mendeliome v1.945 EWSR1 Bryony Thompson Classified gene: EWSR1 as Red List (low evidence)
Mendeliome v1.945 EWSR1 Bryony Thompson Added comment: Comment on list classification: Disputed gene-disease validity assessment by ClinGen ALS spectrum disorders GCEP - 11/10/2022
Mendeliome v1.945 EWSR1 Bryony Thompson Gene: ewsr1 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.177 ERBB4 Bryony Thompson Classified gene: ERBB4 as Amber List (moderate evidence)
Motor Neurone Disease v0.177 ERBB4 Bryony Thompson Added comment: Comment on list classification: Limited gene-disease validity assessment by ClinGen ALS spectrum disorder GCEP - 30/09/2021
Motor Neurone Disease v0.177 ERBB4 Bryony Thompson Gene: erbb4 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.176 DAO Bryony Thompson Deleted their comment
Motor Neurone Disease v0.176 DAO Bryony Thompson Classified gene: DAO as Red List (low evidence)
Motor Neurone Disease v0.176 DAO Bryony Thompson Added comment: Comment on list classification: Refuted gene-disease validity assessment by ClinGen ALS spectrum disorders GCEP - 21/04/2022
Motor Neurone Disease v0.176 DAO Bryony Thompson Gene: dao has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.176 DAO Bryony Thompson Classified gene: DAO as Red List (low evidence)
Motor Neurone Disease v0.176 DAO Bryony Thompson Added comment: Comment on list classification: Refuted gene-disease vailidity assessment by ClinGen ALS spectrum disorders GCEP - 21/04/2022
Motor Neurone Disease v0.176 DAO Bryony Thompson Gene: dao has been classified as Red List (Low Evidence).
Early-onset Dementia v0.160 CCNF Bryony Thompson Classified gene: CCNF as Amber List (moderate evidence)
Early-onset Dementia v0.160 CCNF Bryony Thompson Added comment: Comment on list classification: Limited gene-disease validity assessment by ClinGen ALS spectrum disorders GCEP - 05/04/2022
Early-onset Dementia v0.160 CCNF Bryony Thompson Gene: ccnf has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.175 CCNF Bryony Thompson Classified gene: CCNF as Amber List (moderate evidence)
Motor Neurone Disease v0.175 CCNF Bryony Thompson Added comment: Comment on list classification: Limited gene-disease validity assessment by ClinGen ALS spectrum disorders GCEP - 05/04/2022
Motor Neurone Disease v0.175 CCNF Bryony Thompson Gene: ccnf has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.174 ARPP21 Bryony Thompson gene: ARPP21 was added
gene: ARPP21 was added to Motor Neurone Disease. Sources: ClinGen
Mode of inheritance for gene: ARPP21 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARPP21 were set to 30811981; 31653410; 35525134
Phenotypes for gene: ARPP21 were set to amyotrophic lateral sclerosis MONDO:0004976
Review for gene: ARPP21 was set to RED
Added comment: Limited gene-disease validity classification by ClinGen ALS spectrum disorders GCEP - 10/01/2023
Sources: ClinGen
Motor Neurone Disease v0.173 ANG Bryony Thompson Classified gene: ANG as Red List (low evidence)
Motor Neurone Disease v0.173 ANG Bryony Thompson Gene: ang has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.172 ANG Bryony Thompson Deleted their comment
Motor Neurone Disease v0.172 ANG Bryony Thompson Classified gene: ANG as Amber List (moderate evidence)
Motor Neurone Disease v0.172 ANG Bryony Thompson Added comment: Comment on list classification: Limited gene-disease validity classification by ClinGen ALS GCEP - 08/02/2022
Motor Neurone Disease v0.172 ANG Bryony Thompson Gene: ang has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.171 ANG Bryony Thompson Classified gene: ANG as Amber List (moderate evidence)
Motor Neurone Disease v0.171 ANG Bryony Thompson Added comment: Comment on list classification: Limited gene-disease validity classification by ClinGen ALS GCEP - 08/02/2022
Motor Neurone Disease v0.171 ANG Bryony Thompson Gene: ang has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.170 SPTLC1 Bryony Thompson Marked gene: SPTLC1 as ready
Motor Neurone Disease v0.170 SPTLC1 Bryony Thompson Gene: sptlc1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.170 SPTLC1 Bryony Thompson Classified gene: SPTLC1 as Green List (high evidence)
Motor Neurone Disease v0.170 SPTLC1 Bryony Thompson Gene: sptlc1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.169 SPTLC1 Bryony Thompson gene: SPTLC1 was added
gene: SPTLC1 was added to Motor Neurone Disease. Sources: Literature
Mode of inheritance for gene: SPTLC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTLC1 were set to 34059824; 35900868; 34459874
Phenotypes for gene: SPTLC1 were set to juvenile amyotrophic lateral sclerosis MONDO:0017593
Mode of pathogenicity for gene: SPTLC1 was set to Other
Review for gene: SPTLC1 was set to GREEN
Added comment: At least 10 unrelated probands/families reported with typically juvenile-onset ALS with missense or in-frame indels. Supporting in vitro functional assays demonstrate the mechanism of disease results in unregulated SPT activity and elevated levels of canonical SPT products, in contrast to the mechanism of disease for SPTLC1 variants that cause hereditary sensory and autonomic neuropathy (shift SPT amino acid usage from serine to alanine, resulting in elevated levels of deoxysphingolipids).
Sources: Literature
Mendeliome v1.944 STAG2 Achchuthan Shanmugasundram reviewed gene: STAG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28296084, 29263825, 30158690, 31334757, 33014403, 37010288; Phenotypes: Holoprosencephaly 13, X-linked, OMIM:301043, Mullegama-Klein-Martinez syndrome, OMIM:301022; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.944 SMARCA4 Achchuthan Shanmugasundram reviewed gene: SMARCA4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25168959, 37010288; Phenotypes: Coffin-Siris syndrome 4, OMIM:614609; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.168 SMN1 Bryony Thompson Marked gene: SMN1 as ready
Motor Neurone Disease v0.168 SMN1 Bryony Thompson Gene: smn1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.168 SMN1 Bryony Thompson Classified gene: SMN1 as Green List (high evidence)
Motor Neurone Disease v0.168 SMN1 Bryony Thompson Gene: smn1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.166 SMN1 Bryony Thompson gene: SMN1 was added
gene: SMN1 was added to Motor Neurone Disease. Sources: Literature
Mode of inheritance for gene: SMN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMN1 were set to 20301623
Phenotypes for gene: SMN1 were set to Spinal muscular atrophy-1, MIM# 253300
Added comment: Differential diagnosis for ALS
Sources: Literature
Mendeliome v1.944 XYLT1 Elena Savva Mode of inheritance for gene: XYLT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.943 POGZ Achchuthan Shanmugasundram changed review comment from: Although there are more than three unrelated cases reported with either cleft palate or bifid uvula in total, this phenotype is not consistently present in patients with monoallelic variants in POGZ gene. Hence, this gene should only be added with amber rating in 'Clefting disorders panel'.

PMID:26739615 - Five unrelated individuals were identified with de novo truncating variants in POGZ gene, of which one individual had cleft palate and another one had bifid uvula.

PMID:31782611 - In this cohort of 22 individuals with 21 different loss of function variants in POGZ, two patients were reported with bifid uvula.

DECIPHER database - Of 42 patients with heterozygous sequence variants, one had cleft palate and another one had bifid uvula (PMID:37010288).

The OMIM entry for White-Sutton syndrome (MIM #616364) does not currently include cleft lip/ palate as one of the clinical manifestations of this syndrome.; to: Although there are more than three unrelated cases reported with either cleft palate or bifid uvula in total, this phenotype is not consistently present in patients with monoallelic variants in POGZ gene. Hence, this gene should only be added with amber rating in 'Clefting disorders' panel.

PMID:26739615 - Five unrelated individuals were identified with de novo truncating variants in POGZ gene, of which one individual had cleft palate and another one had bifid uvula.

PMID:31782611 - In this cohort of 22 individuals with 21 different loss of function variants in POGZ, two patients were reported with bifid uvula.

DECIPHER database - Of 42 patients with heterozygous sequence variants, one had cleft palate and another one had bifid uvula (PMID:37010288).

The OMIM entry for White-Sutton syndrome (MIM #616364) does not currently include cleft lip/ palate as one of the clinical manifestations of this syndrome.
Mendeliome v1.943 POGZ Achchuthan Shanmugasundram reviewed gene: POGZ: Rating: AMBER; Mode of pathogenicity: None; Publications: 26739615, 31782611, 37010288; Phenotypes: White-Sutton syndrome, OMIM:616364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.88 TUBB2A Luisa Weiss gene: TUBB2A was added
gene: TUBB2A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TUBB2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB2A were set to 33528536; 24702957
Phenotypes for gene: TUBB2A were set to Cortical dysplasia, complex, with other brain malformations MIM# 615763
Review for gene: TUBB2A was set to GREEN
Added comment: 4 individual cases in one large CP cohort study, all of them with de novo missense mutations, Note that 2/4 mutations are p.A248V, which has also been described in a nonverbal and nonambulatory girl with generalized hypotonia and mild brain malformations (dysmorphic corpus callosum). Cushion et al. (PMID 24702957) also did functional work on this variant showing is had an impaired ability to coassemble with endogenous alpha-tubulin subunits and integrate into microtubule polymers.
Sources: Literature
Cerebral Palsy v1.88 TUBB3 Luisa Weiss gene: TUBB3 was added
gene: TUBB3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TUBB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB3 were set to 33528536
Phenotypes for gene: TUBB3 were set to Cortical dysplasia, complex, with other brain malformations MIM#614039; Fibrosis of extraocular muscles, congenital MIM#600638
Review for gene: TUBB3 was set to GREEN
Added comment: 4 individual cases in one large CP cohort study, all with de novo missense mutations predicted to be pathogenic.
Sources: Literature
Neurodegeneration with brain iron accumulation v0.22 ATP7B Shekeeb Mohammad gene: ATP7B was added
gene: ATP7B was added to Neuroferritinopathies. Sources: Literature,Expert list
Mode of inheritance for gene: ATP7B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP7B were set to 27543917; 28376267
Phenotypes for gene: ATP7B were set to dystonia; parkinsonism; psychosis; liver failure; pancreatitis; renal tubular acidosis; dysarthria; dysphagia
gene: ATP7B was marked as current diagnostic
Neurodegeneration with brain iron accumulation v0.22 AP4M1 Shekeeb Mohammad gene: AP4M1 was added
gene: AP4M1 was added to Neuroferritinopathies. Sources: Literature,Expert list
Mode of inheritance for gene: AP4M1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP4M1 were set to 29473051
Phenotypes for gene: AP4M1 were set to progressive spastic tetraparesis; microcephaly; intellectual disabiliy; growth retardation; epilepsy; peripheral neuropathy; brain iron deposition
Review for gene: AP4M1 was set to GREEN
gene: AP4M1 was marked as current diagnostic
Added comment: Sources: Literature, Expert list
Neurodegeneration with brain iron accumulation v0.22 AP1S2 Shekeeb Mohammad gene: AP1S2 was added
gene: AP1S2 was added to Neuroferritinopathies. Sources: Expert list,Literature
Mode of inheritance for gene: AP1S2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: AP1S2 were set to 23756445
Phenotypes for gene: AP1S2 were set to spasticity; hypotonia; intellectual disability; posterior fossa malformation; brain iron deposition
Penetrance for gene: AP1S2 were set to Complete
Review for gene: AP1S2 was set to GREEN
Added comment: Sources: Expert list, Literature
Facial papules v1.0 Bryony Thompson promoted panel to version 1.0
Facial papules v0.49 Bryony Thompson Panel status changed from internal to public
Panel types changed to Royal Melbourne Hospital; Rare Disease
Mendeliome v1.943 PGAP3 Achchuthan Shanmugasundram reviewed gene: PGAP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28390064, 37010288; Phenotypes: Hyperphosphatasia with impaired intellectual development syndrome 4, OMIM:615716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.943 KMT2A Achchuthan Shanmugasundram reviewed gene: KMT2A: Rating: AMBER; Mode of pathogenicity: None; Publications: 25929198, 30305169, 31710778, 37010288; Phenotypes: Wiedemann-Steiner syndrome, OMIM:605130; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting disorders v0.196 KAT6B Achchuthan Shanmugasundram reviewed gene: KAT6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32424177, 37010288; Phenotypes: Genitopatellar syndrome, OMIM:606170, SBBYSS syndrome, OMIM:603736; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.943 GLI2 Achchuthan Shanmugasundram reviewed gene: GLI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24744436, 37010288; Phenotypes: Culler-Jones syndrome, OMIM:615849, Holoprosencephaly 9, OMIM:610829; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.18 SMAD4 Bryony Thompson Classified gene: SMAD4 as Red List (low evidence)
Pulmonary Arterial Hypertension v1.18 SMAD4 Bryony Thompson Added comment: Comment on list classification: Disputed classification by ClinGen PH GCEP 21/11/2022
Pulmonary Arterial Hypertension v1.18 SMAD4 Bryony Thompson Gene: smad4 has been classified as Red List (Low Evidence).
Pulmonary Arterial Hypertension v1.17 SMAD1 Bryony Thompson Classified gene: SMAD1 as Red List (low evidence)
Pulmonary Arterial Hypertension v1.17 SMAD1 Bryony Thompson Added comment: Comment on list classification: Disputed gene curation by ClinGen PH VCEP 21/11/2022
Pulmonary Arterial Hypertension v1.17 SMAD1 Bryony Thompson Gene: smad1 has been classified as Red List (Low Evidence).
Pulmonary Arterial Hypertension v1.16 GGCX Bryony Thompson Marked gene: GGCX as ready
Pulmonary Arterial Hypertension v1.16 GGCX Bryony Thompson Gene: ggcx has been classified as Amber List (Moderate Evidence).
Pulmonary Arterial Hypertension v1.16 GGCX Bryony Thompson Classified gene: GGCX as Amber List (moderate evidence)
Pulmonary Arterial Hypertension v1.16 GGCX Bryony Thompson Gene: ggcx has been classified as Amber List (Moderate Evidence).
Pulmonary Arterial Hypertension v1.15 GGCX Bryony Thompson gene: GGCX was added
gene: GGCX was added to Pulmonary Arterial Hypertension. Sources: ClinGen
Mode of inheritance for gene: GGCX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GGCX were set to 31727138
Phenotypes for gene: GGCX were set to pulmonary arterial hypertension MONDO:0015924
Review for gene: GGCX was set to AMBER
Added comment: Moderate gene-disease validity classification by the pulmonary hypertension GCEP (4/11/2022). All the genetic evidence is based on one study conducting a gene-based association analysis using 812 European IPAH cases and 12,771 European controls. There were 18 probands with GGCX variants identified.
Sources: ClinGen
Facial papules v0.48 ANTXR2 Bryony Thompson Marked gene: ANTXR2 as ready
Facial papules v0.48 ANTXR2 Bryony Thompson Gene: antxr2 has been classified as Green List (High Evidence).
Facial papules v0.48 ANTXR2 Bryony Thompson Classified gene: ANTXR2 as Green List (high evidence)
Facial papules v0.48 ANTXR2 Bryony Thompson Gene: antxr2 has been classified as Green List (High Evidence).
Facial papules v0.47 ANTXR2 Bryony Thompson gene: ANTXR2 was added
gene: ANTXR2 was added to Facial papules. Sources: Literature
Mode of inheritance for gene: ANTXR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANTXR2 were set to 20301698
Phenotypes for gene: ANTXR2 were set to hyaline fibromatosis syndrome MONDO:0009229
Review for gene: ANTXR2 was set to GREEN
gene: ANTXR2 was marked as current diagnostic
Added comment: Coarse facies and pearly papules on the face are common features of the condition.
Sources: Literature
Facial papules v0.46 IDS Bryony Thompson Marked gene: IDS as ready
Facial papules v0.46 IDS Bryony Thompson Gene: ids has been classified as Green List (High Evidence).
Facial papules v0.46 IDS Bryony Thompson Classified gene: IDS as Green List (high evidence)
Facial papules v0.46 IDS Bryony Thompson Gene: ids has been classified as Green List (High Evidence).
Facial papules v0.45 IDS Bryony Thompson gene: IDS was added
gene: IDS was added to Facial papules. Sources: Expert list
Mode of inheritance for gene: IDS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: IDS were set to 20301451
Phenotypes for gene: IDS were set to Mucopolysaccharidosis type 2 MONDO:0010674
Review for gene: IDS was set to GREEN
gene: IDS was marked as current diagnostic
Added comment: Coarse facies is a feature of mucopolysaccharidosis type 2
Sources: Expert list
Facial papules v0.44 IDUA Bryony Thompson Marked gene: IDUA as ready
Facial papules v0.44 IDUA Bryony Thompson Gene: idua has been classified as Green List (High Evidence).
Facial papules v0.44 IDUA Bryony Thompson Classified gene: IDUA as Green List (high evidence)
Facial papules v0.44 IDUA Bryony Thompson Gene: idua has been classified as Green List (High Evidence).
Facial papules v0.43 IDUA Bryony Thompson gene: IDUA was added
gene: IDUA was added to Facial papules. Sources: Expert list
Mode of inheritance for gene: IDUA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IDUA were set to 20301341
Phenotypes for gene: IDUA were set to Mucopolysaccharidosis type 1 MONDO:0001586
Review for gene: IDUA was set to GREEN
gene: IDUA was marked as current diagnostic
Added comment: Coarse facies is prevalent in severe mucopolysaccharidosis and can be present to a lesser degree in attenuated mucopolysaccharidosis.
Sources: Expert list
Cerebral Palsy v1.88 MSL3 Luisa Weiss gene: MSL3 was added
gene: MSL3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MSL3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: MSL3 were set to 33173220
Phenotypes for gene: MSL3 were set to Basilicata-Akhtar syndrome MIM#301032
Review for gene: MSL3 was set to GREEN
Added comment: Brunet et al. defined the clinical phenotype of 25 patients with MSL3 mutations, three of which had initially been diagnosed as having cerebral palsy.
Sources: Literature
Cerebral Palsy v1.88 MOCS2 Luisa Weiss gene: MOCS2 was added
gene: MOCS2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MOCS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOCS2 were set to 33528536; 22759696
Phenotypes for gene: MOCS2 were set to Molybdenum cofactor deficiency B MIM#252160
Review for gene: MOCS2 was set to GREEN
Added comment: Two patients in a large CP cohort presenting with cerebral palsy. In addition one case report with a patient initially diagnosed as having CP and later found to have biallelic MOCS2 mutations.
Sources: Literature
Cerebral Palsy v1.88 MOCS1 Luisa Weiss reviewed gene: MOCS1: Rating: AMBER; Mode of pathogenicity: None; Publications: 34788679, 27289259; Phenotypes: Molybdenum cofactor deficiency A MIM#252150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.88 MOCS1 Luisa Weiss Deleted their review
Cerebral Palsy v1.88 MEF2C Luisa Weiss gene: MEF2C was added
gene: MEF2C was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MEF2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MEF2C were set to 20412115; 25817843; 33528536
Phenotypes for gene: MEF2C were set to Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language MIM#613443
Review for gene: MEF2C was set to GREEN
Added comment: Two patients in two large CP cohort studies with MEF2C mutations/deletions. In addition, one case report of two patients with MEF2C mutation with one of them diagnosed as having CP.
Sources: Literature
Cerebral Palsy v1.88 MOCS1 Luisa Weiss gene: MOCS1 was added
gene: MOCS1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MOCS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOCS1 were set to 22759696; 34788679
Phenotypes for gene: MOCS1 were set to Molybdenum cofactor deficiency A MIM#252150
Review for gene: MOCS1 was set to AMBER
Added comment: One patient described in a case report diagnosed with cerebral palsy and later re-diagnosed as having molybdenum cofactor deficiency. In addition one more patient in a large CP cohort with biallelic MOCS1 mutation.
Sources: Literature
Cerebral Palsy v1.88 MCOLN1 Luisa Weiss gene: MCOLN1 was added
gene: MCOLN1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MCOLN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCOLN1 were set to 12182165; 21763169
Phenotypes for gene: MCOLN1 were set to Mucolipidosis IV MIM#252650
Review for gene: MCOLN1 was set to GREEN
Added comment: PMID 12182165 presents a case study of 28 patients with Mucolipidosis Type IV. A significant clinical overlap with CP-like encephalopathy is discussed and some of the patients are reported to present with a 'pure non-progressive neurologic deficit'. Other Mucolipidosis Type IV overviews (PMID 21763169) also discuss the clinical similarities and the phenotypic overlap between MLIV and CP.
Sources: Literature
Facial papules v0.42 MLH1 Bryony Thompson Phenotypes for gene: MLH1 were changed from Lynch syndrome MONDO:0005835 to Lynch syndrome MONDO:0005835; Muir-Torre syndrome MONDO:0008018
Facial papules v0.41 MSH2 Bryony Thompson Marked gene: MSH2 as ready
Facial papules v0.41 MSH2 Bryony Thompson Gene: msh2 has been classified as Green List (High Evidence).
Facial papules v0.41 MSH2 Bryony Thompson Classified gene: MSH2 as Green List (high evidence)
Facial papules v0.41 MSH2 Bryony Thompson Gene: msh2 has been classified as Green List (High Evidence).
Facial papules v0.40 MSH2 Bryony Thompson gene: MSH2 was added
gene: MSH2 was added to Facial papules. Sources: Expert list
Mode of inheritance for gene: MSH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MSH2 were set to 20301390; 11231323; 14994245; 15235030; 8931714; 8751876; 9634524
Phenotypes for gene: MSH2 were set to Lynch syndrome MONDO:0005835; Muir-Torre syndrome MONDO:0008018
Review for gene: MSH2 was set to GREEN
gene: MSH2 was marked as current diagnostic
Added comment: The Lynch syndrome variant Muir-Torre syndrome includes sebaceous neoplasms of the skin (including the face) as a main feature of the condition.
Sources: Expert list
Facial papules v0.39 MLH1 Bryony Thompson Marked gene: MLH1 as ready
Facial papules v0.39 MLH1 Bryony Thompson Gene: mlh1 has been classified as Green List (High Evidence).
Facial papules v0.39 MLH1 Bryony Thompson Classified gene: MLH1 as Green List (high evidence)
Facial papules v0.39 MLH1 Bryony Thompson Gene: mlh1 has been classified as Green List (High Evidence).
Facial papules v0.38 MLH1 Bryony Thompson gene: MLH1 was added
gene: MLH1 was added to Facial papules. Sources: Expert list
Mode of inheritance for gene: MLH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MLH1 were set to 20301390; 11231323; 14994245; 15235030; 8931714; 8751876; 9634524
Phenotypes for gene: MLH1 were set to Lynch syndrome MONDO:0005835
Review for gene: MLH1 was set to GREEN
gene: MLH1 was marked as current diagnostic
Added comment: The Lynch syndrome variant Muir-Torre syndrome includes sebaceous neoplasms of the skin (including the face) as a main feature of the condition.
Sources: Expert list
Facial papules v0.37 FH Bryony Thompson Marked gene: FH as ready
Facial papules v0.37 FH Bryony Thompson Gene: fh has been classified as Green List (High Evidence).
Facial papules v0.37 FH Bryony Thompson Classified gene: FH as Green List (high evidence)
Facial papules v0.37 FH Bryony Thompson Gene: fh has been classified as Green List (High Evidence).
Facial papules v0.36 FH Bryony Thompson gene: FH was added
gene: FH was added to Facial papules. Sources: Expert list
Mode of inheritance for gene: FH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FH were set to 20301430
Phenotypes for gene: FH were set to Hereditary leiomyomatosis and renal cell cancer MONDO:0007888
Review for gene: FH was set to GREEN
gene: FH was marked as current diagnostic
Added comment: Cutaneous leiomyomata appear as skin-coloured to light-brown papules as a feature of FH tumour predisposition syndrome and can occasionally occur on the face.
Sources: Expert list
Facial papules v0.35 PTEN Bryony Thompson Marked gene: PTEN as ready
Facial papules v0.35 PTEN Bryony Thompson Gene: pten has been classified as Green List (High Evidence).
Facial papules v0.35 PTEN Bryony Thompson Classified gene: PTEN as Green List (high evidence)
Facial papules v0.35 PTEN Bryony Thompson Gene: pten has been classified as Green List (High Evidence).
Facial papules v0.34 PTEN Bryony Thompson gene: PTEN was added
gene: PTEN was added to Facial papules. Sources: Expert list
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTEN were set to 20301661
Phenotypes for gene: PTEN were set to PTEN hamartoma tumor syndrome MONDO:0017623
Review for gene: PTEN was set to GREEN
gene: PTEN was marked as current diagnostic
Added comment: Multiple facial papules (trichilemmomas) are a diagnostic feature of Cowden syndrome which is included in PTEN hamartoma tumor syndrome.
Sources: Expert list
Facial papules v0.33 APC Bryony Thompson Marked gene: APC as ready
Facial papules v0.33 APC Bryony Thompson Gene: apc has been classified as Green List (High Evidence).
Facial papules v0.33 APC Bryony Thompson Classified gene: APC as Green List (high evidence)
Facial papules v0.33 APC Bryony Thompson Gene: apc has been classified as Green List (High Evidence).
Facial papules v0.32 APC Bryony Thompson gene: APC was added
gene: APC was added to Facial papules. Sources: Expert list
Mode of inheritance for gene: APC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APC were set to 20301519
Phenotypes for gene: APC were set to Classic or attenuated familial adenomatous polyposis MONDO:0021057
Review for gene: APC was set to GREEN
gene: APC was marked as current diagnostic
Added comment: Benign cutaneous lesions on the face including epidermoid cysts and fibromas are extra-intestinal features of FAP
Sources: Expert list
Facial papules v0.31 SUFU Bryony Thompson Marked gene: SUFU as ready
Facial papules v0.31 SUFU Bryony Thompson Gene: sufu has been classified as Green List (High Evidence).
Facial papules v0.31 SUFU Bryony Thompson Classified gene: SUFU as Green List (high evidence)
Facial papules v0.31 SUFU Bryony Thompson Gene: sufu has been classified as Green List (High Evidence).
Facial papules v0.30 SUFU Bryony Thompson gene: SUFU was added
gene: SUFU was added to Facial papules. Sources: Expert list
Mode of inheritance for gene: SUFU was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SUFU were set to 20301330
Phenotypes for gene: SUFU were set to nevoid basal cell carcinoma syndrome MONDO:0007187
Review for gene: SUFU was set to GREEN
gene: SUFU was marked as current diagnostic
Added comment: BCCs can present on the face and coarse facial features and facial milia can also be present but are milder than PTCH1-related NBCCS.
Sources: Expert list
Cerebral Palsy v1.88 MAST1 Luisa Weiss gene: MAST1 was added
gene: MAST1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MAST1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST1 were set to 31700678; 25666757
Phenotypes for gene: MAST1 were set to Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations MIM#618273
Review for gene: MAST1 was set to AMBER
Added comment: Two large CP cohorts, one with one likely pathogenic de novo mutation and two VUS, one of them inherited paternally. The other cohort showed one more case with a de novo missense mutation predicted to be pathogenic. Note that no information is given on the MRI phenotype in these cohorts, so it might be a phenotypic overlap with MIM#618273.
Sources: Literature
Facial papules v0.29 PTCH1 Bryony Thompson Marked gene: PTCH1 as ready
Facial papules v0.29 PTCH1 Bryony Thompson Gene: ptch1 has been classified as Green List (High Evidence).
Facial papules v0.29 PTCH1 Bryony Thompson Classified gene: PTCH1 as Green List (high evidence)
Facial papules v0.29 PTCH1 Bryony Thompson Gene: ptch1 has been classified as Green List (High Evidence).
Facial papules v0.28 PTCH1 Bryony Thompson gene: PTCH1 was added
gene: PTCH1 was added to Facial papules. Sources: Expert list
Mode of inheritance for gene: PTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTCH1 were set to 20301330
Phenotypes for gene: PTCH1 were set to nevoid basal cell carcinoma syndrome MONDO:0007187
Review for gene: PTCH1 was set to GREEN
gene: PTCH1 was marked as current diagnostic
Added comment: BCCs can present on the face and coarse facial features and facial milia are also present in ~60% of cases with a PTCH1 variant.
Sources: Expert list
Facial papules v0.27 HR Bryony Thompson Marked gene: HR as ready
Facial papules v0.27 HR Bryony Thompson Gene: hr has been classified as Green List (High Evidence).
Facial papules v0.27 HR Bryony Thompson Classified gene: HR as Green List (high evidence)
Facial papules v0.27 HR Bryony Thompson Gene: hr has been classified as Green List (High Evidence).
Facial papules v0.26 HR Bryony Thompson gene: HR was added
gene: HR was added to Facial papules. Sources: Literature
Mode of inheritance for gene: HR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HR were set to 12271294; 9856480; 10205263; 17869066
Phenotypes for gene: HR were set to atrichia with papular lesions MONDO:0008847
Review for gene: HR was set to GREEN
gene: HR was marked as current diagnostic
Added comment: Facial papules can be a feature of the condition.
Sources: Literature
Facial papules v0.25 NF1 Bryony Thompson Marked gene: NF1 as ready
Facial papules v0.25 NF1 Bryony Thompson Gene: nf1 has been classified as Green List (High Evidence).
Facial papules v0.25 NF1 Bryony Thompson Classified gene: NF1 as Green List (high evidence)
Facial papules v0.25 NF1 Bryony Thompson Gene: nf1 has been classified as Green List (High Evidence).
Facial papules v0.24 NF1 Bryony Thompson gene: NF1 was added
gene: NF1 was added to Facial papules. Sources: Literature
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NF1 were set to 23984232; 32298062; 34164111
Phenotypes for gene: NF1 were set to neurofibromatosis type 1 MONDO:0018975
Review for gene: NF1 was set to GREEN
gene: NF1 was marked as current diagnostic
Added comment: Facial papules and facial plexiform neurofibromatosis have been reported as a presenting feature of the condition.
Sources: Literature
Facial papules v0.23 Bryony Thompson Panel name changed from Facial papules and lesions to Facial papules
Facial papules v0.22 FLCN Bryony Thompson Marked gene: FLCN as ready
Facial papules v0.22 FLCN Bryony Thompson Gene: flcn has been classified as Green List (High Evidence).
Facial papules v0.22 FLCN Bryony Thompson Classified gene: FLCN as Green List (high evidence)
Facial papules v0.22 FLCN Bryony Thompson Gene: flcn has been classified as Green List (High Evidence).
Facial papules v0.21 FLCN Bryony Thompson gene: FLCN was added
gene: FLCN was added to Facial papules and lesions. Sources: Expert list
Mode of inheritance for gene: FLCN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FLCN were set to 20301695
Phenotypes for gene: FLCN were set to Birt-Hogg-Dube syndrome MONDO:0007607
Review for gene: FLCN was set to GREEN
gene: FLCN was marked as current diagnostic
Added comment: Multiple facial papules (fibrofolliculomas) are a feature of the condition.
Sources: Expert list
Facial papules v0.20 CYLD Bryony Thompson Marked gene: CYLD as ready
Facial papules v0.20 CYLD Bryony Thompson Gene: cyld has been classified as Green List (High Evidence).
Facial papules v0.20 CYLD Bryony Thompson Classified gene: CYLD as Green List (high evidence)
Facial papules v0.20 CYLD Bryony Thompson Gene: cyld has been classified as Green List (High Evidence).
Facial papules v0.19 CYLD Bryony Thompson gene: CYLD was added
gene: CYLD was added to Facial papules and lesions. Sources: Expert list
Mode of inheritance for gene: CYLD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CYLD were set to 32298062
Phenotypes for gene: CYLD were set to familial cylindromatosis MONDO:0007565
Review for gene: CYLD was set to GREEN
gene: CYLD was marked as current diagnostic
Added comment: Multiple facial papules are a feature of the condition.
Sources: Expert list
Facial papules v0.18 CDKN1B Bryony Thompson Marked gene: CDKN1B as ready
Facial papules v0.18 CDKN1B Bryony Thompson Gene: cdkn1b has been classified as Amber List (Moderate Evidence).
Facial papules v0.18 CDKN1B Bryony Thompson Classified gene: CDKN1B as Amber List (moderate evidence)
Facial papules v0.18 CDKN1B Bryony Thompson Added comment: Comment on list classification: Included as MEN1 differential diagnosis
Facial papules v0.18 CDKN1B Bryony Thompson Gene: cdkn1b has been classified as Amber List (Moderate Evidence).
Facial papules v0.17 CDKN1B Bryony Thompson Classified gene: CDKN1B as Amber List (moderate evidence)
Facial papules v0.17 CDKN1B Bryony Thompson Gene: cdkn1b has been classified as Amber List (Moderate Evidence).
Facial papules v0.16 CDKN1B Bryony Thompson gene: CDKN1B was added
gene: CDKN1B was added to Facial papules and lesions. Sources: Expert list
Mode of inheritance for gene: CDKN1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDKN1B were set to 20301710
Phenotypes for gene: CDKN1B were set to multiple endocrine neoplasia type 4 MONDO:0012552
Review for gene: CDKN1B was set to AMBER
Added comment: Overlapping phenotype with MEN1 with possible association with facial angiofibromas, but I couldn't find any evidence in the literature that these are present in individuals with MEN4.
Sources: Expert list
Facial papules v0.15 RET Bryony Thompson Marked gene: RET as ready
Facial papules v0.15 RET Bryony Thompson Gene: ret has been classified as Green List (High Evidence).
Facial papules v0.15 RET Bryony Thompson Classified gene: RET as Green List (high evidence)
Facial papules v0.15 RET Bryony Thompson Gene: ret has been classified as Green List (High Evidence).
Facial papules v0.14 RET Bryony Thompson gene: RET was added
gene: RET was added to Facial papules and lesions. Sources: Expert list
Mode of inheritance for gene: RET was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RET were set to 20301434
Phenotypes for gene: RET were set to multiple endocrine neoplasia type 2B MONDO:0008082
Mode of pathogenicity for gene: RET was set to Other
Review for gene: RET was set to GREEN
gene: RET was marked as current diagnostic
Added comment: Distinctive facies including lip mucosal neuromas resulting in thick vermilion of the upper and lower lip, and mucosal neuromas of the lips and tongue are characteristic of MEN2B. Gain of function variants mainly involving codon 918 (~95%) cause the condition.
Sources: Expert list
Facial papules v0.13 MEN1 Bryony Thompson Marked gene: MEN1 as ready
Facial papules v0.13 MEN1 Bryony Thompson Gene: men1 has been classified as Green List (High Evidence).
Facial papules v0.13 MEN1 Bryony Thompson Classified gene: MEN1 as Green List (high evidence)
Facial papules v0.13 MEN1 Bryony Thompson Gene: men1 has been classified as Green List (High Evidence).
Facial papules v0.12 MEN1 Bryony Thompson gene: MEN1 was added
gene: MEN1 was added to Facial papules and lesions. Sources: Expert list
Mode of inheritance for gene: MEN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MEN1 were set to 20301710
Phenotypes for gene: MEN1 were set to multiple endocrine neoplasia type 1 MONDO:0007540
Review for gene: MEN1 was set to GREEN
gene: MEN1 was marked as current diagnostic
Added comment: Facial angiofibromas are a non-endocrine tumour that can be present in multiple endocrine neoplasia type 1.
Sources: Expert list
Facial papules v0.11 TSC2 Bryony Thompson Marked gene: TSC2 as ready
Facial papules v0.11 TSC2 Bryony Thompson Gene: tsc2 has been classified as Green List (High Evidence).
Facial papules v0.11 TSC2 Bryony Thompson Classified gene: TSC2 as Green List (high evidence)
Facial papules v0.11 TSC2 Bryony Thompson Gene: tsc2 has been classified as Green List (High Evidence).
Facial papules v0.10 TSC2 Bryony Thompson gene: TSC2 was added
gene: TSC2 was added to Facial papules and lesions. Sources: Expert list
Mode of inheritance for gene: TSC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TSC2 were set to 20301399
Phenotypes for gene: TSC2 were set to tuberous sclerosis MONDO:0001734
Review for gene: TSC2 was set to GREEN
gene: TSC2 was marked as current diagnostic
Added comment: Facial angiofibromas are a characteristic feature of the tuberous sclerosis
Sources: Expert list
Facial papules v0.9 TSC1 Bryony Thompson Marked gene: TSC1 as ready
Facial papules v0.9 TSC1 Bryony Thompson Gene: tsc1 has been classified as Green List (High Evidence).
Facial papules v0.9 TSC1 Bryony Thompson Classified gene: TSC1 as Green List (high evidence)
Facial papules v0.9 TSC1 Bryony Thompson Gene: tsc1 has been classified as Green List (High Evidence).
Facial papules v0.8 TSC1 Bryony Thompson gene: TSC1 was added
gene: TSC1 was added to Facial papules and lesions. Sources: Expert list
Mode of inheritance for gene: TSC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TSC1 were set to 20301399
Phenotypes for gene: TSC1 were set to tuberous sclerosis MONDO:0001734
Review for gene: TSC1 was set to GREEN
gene: TSC1 was marked as current diagnostic
Added comment: Facial angiofibromas are a characteristic feature of the tuberous sclerosis
Sources: Expert list
Facial papules v0.7 Bryony Thompson Panel name changed from Facial papules to Facial papules and lesions
Facial papules v0.6 ECM1 Bryony Thompson Marked gene: ECM1 as ready
Facial papules v0.6 ECM1 Bryony Thompson Gene: ecm1 has been classified as Green List (High Evidence).
Facial papules v0.6 ECM1 Bryony Thompson Classified gene: ECM1 as Green List (high evidence)
Facial papules v0.6 ECM1 Bryony Thompson Gene: ecm1 has been classified as Green List (High Evidence).
Facial papules v0.5 ECM1 Bryony Thompson gene: ECM1 was added
gene: ECM1 was added to Facial papules. Sources: Expert list
Mode of inheritance for gene: ECM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ECM1 were set to 26803878
Phenotypes for gene: ECM1 were set to lipoid proteinosis MONDO:0009530
Review for gene: ECM1 was set to GREEN
gene: ECM1 was marked as current diagnostic
Added comment: One of the predominant features of lipoid proteinosis is multiple beaded papules along the eyelid margins and inner canthus known as moniliform blepharosis.
Sources: Expert list
Facial papules v0.4 ATP2A2 Bryony Thompson Marked gene: ATP2A2 as ready
Facial papules v0.4 ATP2A2 Bryony Thompson Gene: atp2a2 has been classified as Green List (High Evidence).
Facial papules v0.4 ATP2A2 Bryony Thompson Classified gene: ATP2A2 as Green List (high evidence)
Facial papules v0.4 ATP2A2 Bryony Thompson Gene: atp2a2 has been classified as Green List (High Evidence).
Facial papules v0.3 ATP2A2 Bryony Thompson gene: ATP2A2 was added
gene: ATP2A2 was added to Facial papules. Sources: Expert list
Mode of inheritance for gene: ATP2A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP2A2 were set to 10080178; 31911771
Phenotypes for gene: ATP2A2 were set to Darier disease MONDO:0007417
Review for gene: ATP2A2 was set to GREEN
gene: ATP2A2 was marked as current diagnostic
Added comment: Papules on the seborrheic areas of the head and neck are a predominant feature of Darier disease.
Sources: Expert list
Facial papules v0.2 ABCC6 Bryony Thompson Marked gene: ABCC6 as ready
Facial papules v0.2 ABCC6 Bryony Thompson Gene: abcc6 has been classified as Green List (High Evidence).
Facial papules v0.2 ABCC6 Bryony Thompson Classified gene: ABCC6 as Green List (high evidence)
Facial papules v0.2 ABCC6 Bryony Thompson Gene: abcc6 has been classified as Green List (High Evidence).
Facial papules v0.1 ABCC6 Bryony Thompson gene: ABCC6 was added
gene: ABCC6 was added to Facial papules. Sources: Expert list
Mode of inheritance for gene: ABCC6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCC6 were set to 20301292
Phenotypes for gene: ABCC6 were set to autosomal recessive inherited pseudoxanthoma elasticum MONDO:0009925
Review for gene: ABCC6 was set to GREEN
gene: ABCC6 was marked as current diagnostic
Added comment: The primary skin lesions present in pseudoxanthoma elasticum are papules that often develop on the lateral aspect of the neck.
Sources: Expert list
Facial papules v0.0 Bryony Thompson Added Panel Facial papules
Set list of related panels to Papule HP:0200034
Set panel types to: Royal Melbourne Hospital
Mendeliome v1.943 FGFR3 Achchuthan Shanmugasundram reviewed gene: FGFR3: Rating: AMBER; Mode of pathogenicity: None; Publications: 22565872, 29150894, 37010288; Phenotypes: Muenke syndrome, OMIM:602849, Hypochondroplasia, OMIM:146000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Spastic Paraplegia - paediatric v1.66 SPTSSA Zornitza Stark Phenotypes for gene: SPTSSA were changed from complex hereditary spastic paraplegia, MONDO:0015150 to Spastic paraplegia 90B, autosomal recessive , MIM# 620417; Spastic paraplegia 90A, autosomal dominant, MIM# 620416
Hereditary Spastic Paraplegia - paediatric v1.65 SPTSSA Zornitza Stark edited their review of gene: SPTSSA: Changed rating: AMBER
Hereditary Spastic Paraplegia - paediatric v1.65 SPTSSA Zornitza Stark edited their review of gene: SPTSSA: Changed rating: GREEN
Hereditary Spastic Paraplegia - paediatric v1.65 SPTSSA Zornitza Stark reviewed gene: SPTSSA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 90B, autosomal recessive , MIM# 620417, Spastic paraplegia 90A, autosomal dominant, MIM# 620416; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.943 SPTSSA Zornitza Stark Phenotypes for gene: SPTSSA were changed from complex hereditary spastic paraplegia, MONDO:0015150 to Spastic paraplegia 90B, autosomal recessive , MIM# 620417; Spastic paraplegia 90A, autosomal dominant, MIM# 620416
Mendeliome v1.942 SPTSSA Zornitza Stark reviewed gene: SPTSSA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 90B, autosomal recessive , MIM# 620417, Spastic paraplegia 90A, autosomal dominant, MIM# 620416; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinitis pigmentosa_Autosomal Dominant v0.57 VWA8 Zornitza Stark Phenotypes for gene: VWA8 were changed from Retinitis pigmentosa (MONDO:0019200), VWA8-related to Retinitis pigmentosa 97, MIM#620422
Retinitis pigmentosa_Autosomal Dominant v0.56 VWA8 Zornitza Stark reviewed gene: VWA8: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 97, MIM#620422; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.942 VWA8 Zornitza Stark Phenotypes for gene: VWA8 were changed from Retinitis pigmentosa (MONDO:0019200), VWA8-related to Retinitis pigmentosa 97, MIM#620422
Mendeliome v1.941 VWA8 Zornitza Stark reviewed gene: VWA8: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 97, MIM#620422; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.941 ARID1B Achchuthan Shanmugasundram changed review comment from: There are at least three unrelated cases with monoallelic variants in ARID1B gene reported with either cleft palate, cleft uvula or bifid uvula. Hence, this gene can be added with green rating in the Clefting disorders panel.

PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

One patient with ARID1B variant (c.3183_3184​insT/ p.Tyr1062LeufsTer10) was reported with submucous cleft soft palate and two patients with ARID1B variants (c.4155_4156​insA/ p.Asn1386LysfsTer18 & c.2620+5G​>A) were reported with bifid uvula in DECIPHER database.; to: Although there are more than three unrelated cases with ARID1B monoallelic variants reported with either cleft palate, cleft uvula or bifid uvula, clefting isn not consistently present in patients with ARID1B variants. Hence, this gene can be added with amber rating in the Clefting disorders panel.

PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

Of >100 patients with ARID1B variants in the DECIPHER database, only one patient (c.3183_3184​insT/ p.Tyr1062LeufsTer10) was reported with submucous cleft soft palate and two patients (c.4155_4156​insA/ p.Asn1386LysfsTer18 & c.2620+5G​>A) were reported with bifid uvula.
Mendeliome v1.941 ARID1B Achchuthan Shanmugasundram edited their review of gene: ARID1B: Changed rating: AMBER
Mendeliome v1.941 CHD4 Achchuthan Shanmugasundram changed review comment from: This gene should be added to the Clefting disorders panel with a green rating as there are four unrelated cases presenting with either cleft palate and/or bifid uvula.

PMID:3138819 reported a patient with heterozygous variant (p.Gln715Ter) in CHD4 that had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, DDD study reported two patients with likely pathogenic heterozygous variants who had cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288); to: Although there are four unrelated cases presenting with either cleft palate and/or bifid uvula, this phenotype is not consistent among patients identified with monoallelic variants in CHD4 gene. Hence, this gene should be added to the Clefting disorders panel with amber rating.

PMID:31388190 reported 32 patients with heterozygous variants in CHD4 gene, of which one patient (p.Gln715Ter) had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, 2 out of 10 patients with pathogenic/ likely pathogenic heterozygous variants from the DDD study were reported with cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288).
Mendeliome v1.941 CHD4 Achchuthan Shanmugasundram edited their review of gene: CHD4: Changed rating: AMBER
Clefting disorders v0.196 B4GALT7 Achchuthan Shanmugasundram Deleted their review
Clefting disorders v0.196 DDX3X Achchuthan Shanmugasundram Deleted their review
Clefting disorders v0.196 DDX3X Achchuthan Shanmugasundram reviewed gene: DDX3X: Rating: GREEN; Mode of pathogenicity: None; Publications: 26235985, 27159028, 37010288; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, OMIM:300958; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.941 CNTNAP1 Achchuthan Shanmugasundram reviewed gene: CNTNAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28374019, 29511323, 29882456, 37010288; Phenotypes: Hypomyelinating neuropathy, congenital, 3, OMIM:618186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.941 ARID1B Achchuthan Shanmugasundram reviewed gene: ARID1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 30349098, 37010288; Phenotypes: Coffin-Siris syndrome 1, OMIM:135900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ectodermal Dysplasia v0.83 TUFT1 Zornitza Stark Publications for gene: TUFT1 were set to https://doi.org/10.1093/bjd/ljac026
Ectodermal Dysplasia v0.82 TUFT1 Zornitza Stark edited their review of gene: TUFT1: Changed publications: 36689522
Mendeliome v1.941 TUFT1 Zornitza Stark Publications for gene: TUFT1 were set to https://doi.org/10.1093/bjd/ljac026
Mendeliome v1.940 TUFT1 Zornitza Stark edited their review of gene: TUFT1: Changed publications: 36689522
Ectodermal Dysplasia v0.82 TUFT1 Zornitza Stark Phenotypes for gene: TUFT1 were changed from Ectodermal dysplasia, MONDO:0019287, TUFT1-related to Woolly hair-skin fragility syndrome, MIM# 620415
Ectodermal Dysplasia v0.81 TUFT1 Zornitza Stark edited their review of gene: TUFT1: Changed phenotypes: Woolly hair-skin fragility syndrome, MIM# 620415
Mendeliome v1.940 TUFT1 Zornitza Stark Phenotypes for gene: TUFT1 were changed from Ectodermal dysplasia, MONDO:0019287, TUFT1-related to Woolly hair-skin fragility syndrome, MIM# 620415
Mendeliome v1.939 TUFT1 Zornitza Stark edited their review of gene: TUFT1: Changed phenotypes: Woolly hair-skin fragility syndrome, MIM# 620415
Mendeliome v1.939 CHD4 Achchuthan Shanmugasundram reviewed gene: CHD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31388190, 37010288; Phenotypes: Sifrim-Hitz-Weiss syndrome, OMIM:617159; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting disorders v0.196 B4GALT7 Achchuthan Shanmugasundram reviewed gene: B4GALT7: Rating: GREEN; Mode of pathogenicity: None; Publications: 24755949, 26940150, 31278392; Phenotypes: Ehlers-Danlos syndrome, spondylodysplastic type, 1, OMIM:130070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.166 DNAJC3 Sangavi Sivagnanasundram reviewed gene: DNAJC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25466870, 32738013, 34654017; Phenotypes: Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, MIM# 616192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.166 DDHD1 Sangavi Sivagnanasundram reviewed gene: DDHD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23176821; Phenotypes: Spastic paraplegia 28, autosomal recessive, MIM# 609340, MONDO:0012256; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Long QT Syndrome v0.61 CAV3 Daniel Flanagan reviewed gene: CAV3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 31983240, 17060380, 17275750, 30588629; Phenotypes: Long QT syndrome 9 (MIM#611818); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.88 MLC1 Luisa Weiss gene: MLC1 was added
gene: MLC1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MLC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MLC1 were set to 34788679
Phenotypes for gene: MLC1 were set to Megalencephalic leukoencephalopathy with subcortical cysts MIM#604004
Review for gene: MLC1 was set to AMBER
Added comment: One patient in a larger CP cohort harbouring compound heterozygous MLC1 mutations. Phenotypic overlap between MIM#604004 and CP, however, seems small, as MIM#604004 is a progressive neurological disorder with MRI abnormalities.
Sources: Literature
Genetic Epilepsy v0.1864 STXBP1 Michelle Torres reviewed gene: STXBP1: Rating: AMBER; Mode of pathogenicity: Other; Publications: 31855252; Phenotypes: Developmental and epileptic encephalopathy 4, MIM# 612164; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.88 MFN2 Luisa Weiss reviewed gene: MFN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 33528536, 34114234, 34531397; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2A2A MIM#609260, Hereditary motor and sensory neuropathy VIA MIM#601152; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.88 TUBB2B Zornitza Stark Marked gene: TUBB2B as ready
Cerebral Palsy v1.88 TUBB2B Zornitza Stark Gene: tubb2b has been classified as Green List (High Evidence).
Cerebral Palsy v1.88 TUBB2B Zornitza Stark Publications for gene: TUBB2B were set to PMID: 33528536
Cerebral Palsy v1.87 TUBB2B Zornitza Stark Classified gene: TUBB2B as Green List (high evidence)
Cerebral Palsy v1.87 TUBB2B Zornitza Stark Gene: tubb2b has been classified as Green List (High Evidence).
Cerebral Palsy v1.86 TUBB2B Luisa Weiss reviewed gene: TUBB2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536, 34077496; Phenotypes: Cortical dysplasia, complex, with other brain malformations MIM#610031; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.86 WDR26 Luisa Weiss gene: WDR26 was added
gene: WDR26 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: WDR26 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR26 were set to 33528536; 34788679
Phenotypes for gene: WDR26 were set to Skraban-Deardorff syndrome MIM#617616
Review for gene: WDR26 was set to GREEN
Added comment: Two large CP cohort studies with 3 individual patients harbouring de novo missense or nonsense mutations or whole gene deletions in WDR26.
Sources: Literature
Cerebral Palsy v1.86 WWOX Luisa Weiss gene: WWOX was added
gene: WWOX was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: WWOX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WWOX were set to 34540776; 30361190; 33528536
Phenotypes for gene: WWOX were set to Developmental and epileptic encephalopathy MIM#616211; Spinocerebellar ataxia MIM#6143223
Review for gene: WWOX was set to GREEN
Added comment: 2 large CP cohort studies with 4 patients in total harbouring a biallelic WWOX mutation. In addition, case reports of patients with epileptic encephalopathy due to WWOX mutations show significant phenotypic overlap with CP
Sources: Literature
Neuromuscular Superpanel v1.0 Bryony Thompson Added Panel Neuromuscular Superpanel
Set child panels to: Hereditary Spastic Paraplegia - paediatric; Dystonia - isolated/combined; Hereditary Neuropathy_CMT - isolated; Gastrointestinal neuromuscular disease; Limb-Girdle Muscular Dystrophy and Distal Myopathy; Congenital Myasthenia; Ataxia - paediatric; Malignant Hyperthermia Susceptibility; Hereditary Spastic Paraplegia - adult onset; Ataxia - adult onset; Skeletal Muscle Channelopathies; Muscular dystrophy and myopathy_Paediatric; Rhabdomyolysis and Metabolic Myopathy; Arthrogryposis; Dystonia - complex; Hereditary Neuropathy - complex; Motor Neurone Disease; Paroxysmal Dyskinesia
Set panel types to: Superpanel; Royal Melbourne Hospital
Hereditary Spastic Paraplegia - adult onset v1.6 GFAP Bryony Thompson Marked gene: GFAP as ready
Hereditary Spastic Paraplegia - adult onset v1.6 GFAP Bryony Thompson Gene: gfap has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - adult onset v1.6 GFAP Bryony Thompson Classified gene: GFAP as Green List (high evidence)
Hereditary Spastic Paraplegia - adult onset v1.6 GFAP Bryony Thompson Gene: gfap has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - adult onset v1.5 GFAP Bryony Thompson gene: GFAP was added
gene: GFAP was added to Hereditary Spastic Paraplegia - adult onset. Sources: Literature
Mode of inheritance for gene: GFAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GFAP were set to 11138011; 18684770
Phenotypes for gene: GFAP were set to Alexander disease MONDO:0008752
Mode of pathogenicity for gene: GFAP was set to Other
Review for gene: GFAP was set to GREEN
gene: GFAP was marked as current diagnostic
Added comment: Spastic paraparesis/spasticity has been reported as a prevalent feature of the adult form of the disease.
Sources: Literature
Callosome v0.494 MLH1 Chirag Patel Classified gene: MLH1 as Red List (low evidence)
Callosome v0.494 MLH1 Chirag Patel Gene: mlh1 has been classified as Red List (Low Evidence).
Callosome v0.493 MSH2 Chirag Patel Classified gene: MSH2 as Red List (low evidence)
Callosome v0.493 MSH2 Chirag Patel Gene: msh2 has been classified as Red List (Low Evidence).
Callosome v0.492 MSH6 Chirag Patel Classified gene: MSH6 as Red List (low evidence)
Callosome v0.492 MSH6 Chirag Patel Gene: msh6 has been classified as Red List (Low Evidence).
Leukodystrophy - adult onset v0.109 ACTA2 Bryony Thompson Marked gene: ACTA2 as ready
Leukodystrophy - adult onset v0.109 ACTA2 Bryony Thompson Gene: acta2 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.109 ACTA2 Bryony Thompson Classified gene: ACTA2 as Green List (high evidence)
Leukodystrophy - adult onset v0.109 ACTA2 Bryony Thompson Gene: acta2 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.108 ACTA2 Bryony Thompson gene: ACTA2 was added
gene: ACTA2 was added to Leukodystrophy - adult onset. Sources: Literature
Mode of inheritance for gene: ACTA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTA2 were set to 29300374
Phenotypes for gene: ACTA2 were set to multisystemic smooth muscle dysfunction syndrome MONDO:0013452
Mode of pathogenicity for gene: ACTA2 was set to Other
Review for gene: ACTA2 was set to GREEN
gene: ACTA2 was marked as current diagnostic
Added comment: Hyperintense periventricular white matter lesions were present in 95% (21/22) of smooth muscle dysfunction syndrome cases with missense variants involving Arg179. Age of diagnosis varied from infancy to adulthood.
Sources: Literature
Leukodystrophy - paediatric v0.289 ACTA2 Bryony Thompson Marked gene: ACTA2 as ready
Leukodystrophy - paediatric v0.289 ACTA2 Bryony Thompson Gene: acta2 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.289 ACTA2 Bryony Thompson Classified gene: ACTA2 as Green List (high evidence)
Leukodystrophy - paediatric v0.289 ACTA2 Bryony Thompson Gene: acta2 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.288 ACTA2 Bryony Thompson gene: ACTA2 was added
gene: ACTA2 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: ACTA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTA2 were set to 29300374
Phenotypes for gene: ACTA2 were set to multisystemic smooth muscle dysfunction syndrome MONDO:0013452
Mode of pathogenicity for gene: ACTA2 was set to Other
Review for gene: ACTA2 was set to GREEN
gene: ACTA2 was marked as current diagnostic
Added comment: Hyperintense periventricular white matter lesions were present in 95% (21/22) of smooth muscle dysfunction syndrome cases with missense variants involving Arg179. Age of diagnosis varied from infancy to adulthood.
Sources: Literature
Cerebral Palsy v1.86 MAP2K1 Luisa Weiss edited their review of gene: MAP2K1: Changed rating: GREEN
Cerebral Palsy v1.86 MAP2K1 Luisa Weiss gene: MAP2K1 was added
gene: MAP2K1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MAP2K1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP2K1 were set to 33528536
Phenotypes for gene: MAP2K1 were set to Cardiofaciocutaneous syndrome MIM#615279
Added comment: Four individual cases in one large CP cohort study. All of them missense and confirmed de novo. Note that the c.A389G,p.Y130C mutation affected 3/4 patients and seems to be a recurrent mutation. This mutation has also been described in patients with cardiofaciocutanuous syndrome.
Sources: Literature
Cerebral Palsy v1.86 KMT2B Luisa Weiss reviewed gene: KMT2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536, 25666757; Phenotypes: Dystonia 28, childhood-onset MIM#617284, Intellectual developmental disorder, autosomal dominant MIM#619934; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.86 KCNT1 Luisa Weiss gene: KCNT1 was added
gene: KCNT1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KCNT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNT1 were set to 33528536; 34788679
Phenotypes for gene: KCNT1 were set to Developmental and epileptic encephalopathy MIM#614959
Review for gene: KCNT1 was set to GREEN
Added comment: 4 cases in two large CP cohort studies. All of them are missense mutations, mostly confirmed de novo mutations.
Sources: Literature
Cerebral Palsy v1.86 KCNB1 Luisa Weiss gene: KCNB1 was added
gene: KCNB1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KCNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB1 were set to 33528536; 34788679
Phenotypes for gene: KCNB1 were set to Developmental and epileptic encephalopathy MIM#616056
Review for gene: KCNB1 was set to AMBER
Added comment: One case each in two large CP cohort studies with heterozygous missense mutations, only one of the mutations confirmed de novo.
Sources: Literature
Cerebral Palsy v1.86 KAT6A Luisa Weiss gene: KAT6A was added
gene: KAT6A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KAT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KAT6A were set to 33528536
Phenotypes for gene: KAT6A were set to Arboleda-Tham syndrome MIM#616268
Review for gene: KAT6A was set to GREEN
Added comment: Several cases in a large CP cohort study with Loss of function mutations in KAT6A, all mutations confrimed de novo
Sources: Literature
Cerebral Palsy v1.86 IRF2BPL Luisa Weiss gene: IRF2BPL was added
gene: IRF2BPL was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: IRF2BPL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRF2BPL were set to 30057031; 30166628
Phenotypes for gene: IRF2BPL were set to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures MIM#618088
Review for gene: IRF2BPL was set to GREEN
Added comment: Two large IRF2BPL cohort studies, in one study (PMID:30166628) two children had previously been described with different forms of CP and later found to have a frameshift IRF2BPL mutation. In the other publication (PMID:3005703) there was significant phenotypic overlap with spasticity and non-progressive movemetn disorder, even though no formal CP diagnosis had been made.
Sources: Literature
Cerebral Palsy v1.86 IQSEC2 Luisa Weiss reviewed gene: IQSEC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536; Phenotypes: Intellectual developmental disorder MIM#09530; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hereditary Spastic Paraplegia - paediatric v1.65 GFAP Bryony Thompson Marked gene: GFAP as ready
Hereditary Spastic Paraplegia - paediatric v1.65 GFAP Bryony Thompson Gene: gfap has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.65 GFAP Bryony Thompson Classified gene: GFAP as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v1.65 GFAP Bryony Thompson Gene: gfap has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.64 GFAP Bryony Thompson gene: GFAP was added
gene: GFAP was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: GFAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GFAP were set to 34146839
Phenotypes for gene: GFAP were set to Alexander disease MONDO:0008752
Review for gene: GFAP was set to GREEN
gene: GFAP was marked as current diagnostic
Added comment: Spasticity was a feature of the condition in 23.9% of an infantile cohort (n=135) with a clinical and genetic diagnosis of Alexander disease
Sources: Expert list
Predominantly Antibody Deficiency v0.125 TCF3 Peter McNaughton reviewed gene: TCF3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37277074; Phenotypes: Hypogammaglobulinaemia; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.20 RYR1 Bryony Thompson Marked gene: RYR1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.20 RYR1 Bryony Thompson Gene: ryr1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.20 RYR1 Bryony Thompson Classified gene: RYR1 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.20 RYR1 Bryony Thompson Gene: ryr1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.19 RYR1 Bryony Thompson gene: RYR1 was added
gene: RYR1 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for gene: RYR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RYR1 were set to 30842289; 33458580
Phenotypes for gene: RYR1 were set to calf predominant distal myopathy; distal myopathy MONDO:0018949
Review for gene: RYR1 was set to GREEN
gene: RYR1 was marked as current diagnostic
Added comment: Distal myopathy has been reported as a presenting feature of both monoallelic and biallelic RYR1-related myopathy
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.18 NEB Bryony Thompson Marked gene: NEB as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.18 NEB Bryony Thompson Gene: neb has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.18 NEB Bryony Thompson Classified gene: NEB as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.18 NEB Bryony Thompson Gene: neb has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.17 NEB Bryony Thompson gene: NEB was added
gene: NEB was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for gene: NEB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEB were set to 21724397; 17525139; 33458580; 25205138
Phenotypes for gene: NEB were set to distal myopathy MONDO:0018949
Review for gene: NEB was set to GREEN
gene: NEB was marked as current diagnostic
Added comment: Distal myopathy has been reported as a presenting feature, mainly in cases with biallelic missense variants.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.16 OPDM1 Bryony Thompson Marked STR: OPDM1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.16 OPDM1 Bryony Thompson Str: opdm1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.16 OPDM1 Bryony Thompson Classified STR: OPDM1 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.16 OPDM1 Bryony Thompson Str: opdm1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.15 OPDM1 Bryony Thompson STR: OPDM1 was added
STR: OPDM1 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Expert list
Mode of inheritance for STR: OPDM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM1 were set to 31332380; 34047774
Phenotypes for STR: OPDM1 were set to Oculopharyngodistal myopathy 1 MIM#164310
Review for STR: OPDM1 was set to GREEN
STR: OPDM1 was marked as clinically relevant
Added comment: NM_013437.5:c.-102CGG[X]
RNA-mediated toxicity is thought to be the mechanism of disease. Sixty-five Japanese patients with oculopharyngodistal myopathy (OPDM) from 59 families with CGG repeat expansions in LRP12. This represents the most common OPDM subtype among all patients in Japan with genetically diagnosed OPDM.
Normal: 13 to 45 repeats.
Pathogenic: 85 to 289 repeats.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.14 OPDM2 Bryony Thompson Marked STR: OPDM2 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.14 OPDM2 Bryony Thompson Str: opdm2 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.14 OPDM2 Bryony Thompson Classified STR: OPDM2 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.14 OPDM2 Bryony Thompson Str: opdm2 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.13 OPDM2 Bryony Thompson STR: OPDM2 was added
STR: OPDM2 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Expert list
Mode of inheritance for STR: OPDM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM2 were set to 32413282; 33374016
Phenotypes for STR: OPDM2 were set to Oculopharyngodistal myopathy 2 MIM#618940
Review for STR: OPDM2 was set to GREEN
STR: OPDM2 was marked as clinically relevant
Added comment: NM_005716.4:c.-211GGC[X]
>15 Chinese families/probands with a heterozygous trinucleotide repeat expansion (CGG(n)) in 5'UTR exon 1 of the GIPC1 gene. The expansion was found by a combination of linkage analysis, whole-exome sequencing, long-range sequencing, and PCR analysis, and segregated with the disorder in the family. Repeat lengths in the patients ranged from 70 to 138. Normal repeat lengths ranged from 12 to 32.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.12 NIID Bryony Thompson Marked STR: NIID as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.12 NIID Bryony Thompson Str: niid has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.12 NIID Bryony Thompson Classified STR: NIID as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.12 NIID Bryony Thompson Str: niid has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.11 NIID Bryony Thompson STR: NIID was added
STR: NIID was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Expert list
Mode of inheritance for STR: NIID was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: NIID were set to 31178126; 31332381; 31819945; 33887199; 33943039; 32250060; 31332380; 32852534; 32989102; 34333668
Phenotypes for STR: NIID were set to Neuronal intranuclear inclusion disease MIM#603472; Oculopharyngodistal myopathy 3 MIM#619473; Tremor, hereditary essential, 6 MIM#618866
Review for STR: NIID was set to GREEN
STR: NIID was marked as clinically relevant
Added comment: NM_001364012.2:c.-164GGC[X]
Expanded repeat in NOTCH2NLC sequence is (GGC)9(GGA)2(GGC)2.
Large number of families and sporadic cases reported with expansions, with a range of neurodegenerative phenotypes, including: dementia, Parkinsonism/tremor, peripheral neuropathy, leukoencephalopathy, myopathy, motor neurone disease.
Normal repeat range: 4-40, 1 control had 61 repeats and may have been a presymptomatic carrier.
Intermediate range: 41-60 identified in Parkinson's disease
Pathogenic repeat range: >=60-520
Mechanism of disease is translation of repeat expansion into a toxic polyglycine protein, identified in both mouse models and tissue samples from affected individuals.
Sources: Expert list
Mendeliome v1.939 KLHL9 Bryony Thompson Marked gene: KLHL9 as ready
Mendeliome v1.939 KLHL9 Bryony Thompson Gene: klhl9 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.939 KLHL9 Bryony Thompson Classified gene: KLHL9 as Amber List (moderate evidence)
Mendeliome v1.939 KLHL9 Bryony Thompson Gene: klhl9 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.938 KLHL9 Bryony Thompson changed review comment from: A single German family reported in 2010, segregating a missense variant c.796T>C p.Leu95Phe. In vitro functional assays demonstrated the variant diminishes the binding of KLHL9 to Cul3.
Sources: Literature; to: A single German family reported in 2010, segregating a missense variant c.796T>C p.Leu95Phe. In vitro functional assays demonstrated the variant diminishes the binding of KLHL9 to Cul3.
Ankle flexion contracture is reported in a mouse model, but there are other significant features present in the homozygous animals too - https://www.mousephenotype.org/data/genes/MGI:2180122
Sources: Literature
Mendeliome v1.938 KLHL9 Bryony Thompson gene: KLHL9 was added
gene: KLHL9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KLHL9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLHL9 were set to 20554658
Phenotypes for gene: KLHL9 were set to distal myopathy MONDO:0018949
Review for gene: KLHL9 was set to AMBER
Added comment: A single German family reported in 2010, segregating a missense variant c.796T>C p.Leu95Phe. In vitro functional assays demonstrated the variant diminishes the binding of KLHL9 to Cul3.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.10 KLHL9 Bryony Thompson Marked gene: KLHL9 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.10 KLHL9 Bryony Thompson Gene: klhl9 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.10 KLHL9 Bryony Thompson Classified gene: KLHL9 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.10 KLHL9 Bryony Thompson Gene: klhl9 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.9 KLHL9 Bryony Thompson edited their review of gene: KLHL9: Changed publications: 20554658, 33458580
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.9 KLHL9 Bryony Thompson gene: KLHL9 was added
gene: KLHL9 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for gene: KLHL9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLHL9 were set to 20554658
Phenotypes for gene: KLHL9 were set to distal myopathy MONDO:0018949
Review for gene: KLHL9 was set to AMBER
Added comment: A single German family reported in 2010, segregating a missense variant c.796T>C p.Leu95Phe. In vitro functional assays demonstrated the variant diminishes the binding of KLHL9 to Cul3.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.8 HSPB8 Bryony Thompson Marked gene: HSPB8 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.8 HSPB8 Bryony Thompson Gene: hspb8 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.8 HSPB8 Bryony Thompson Classified gene: HSPB8 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.8 HSPB8 Bryony Thompson Gene: hspb8 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.7 HSPB8 Bryony Thompson gene: HSPB8 was added
gene: HSPB8 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for gene: HSPB8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HSPB8 were set to 32165108; 26718575; 31403083; 28780615
Phenotypes for gene: HSPB8 were set to autosomal dominant distal axonal motor neuropathy-myofibrillar myopathy syndrome MONDO:0018773
Mode of pathogenicity for gene: HSPB8 was set to Other
Review for gene: HSPB8 was set to GREEN
gene: HSPB8 was marked as current diagnostic
Added comment: At least 4 reported unrelated families with distal myopathy and a supporting mouse model. Toxic gain of function is the mechanism of disease.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.6 DNM2 Bryony Thompson Marked gene: DNM2 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.6 DNM2 Bryony Thompson Gene: dnm2 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.6 DNM2 Bryony Thompson Classified gene: DNM2 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.6 DNM2 Bryony Thompson Gene: dnm2 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.5 DNM2 Bryony Thompson gene: DNM2 was added
gene: DNM2 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for gene: DNM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNM2 were set to 16227997; 33458580; 30232666; 24465259; 23938035
Phenotypes for gene: DNM2 were set to autosomal dominant centronuclear myopathy MONDO:0008048
Review for gene: DNM2 was set to GREEN
gene: DNM2 was marked as current diagnostic
Added comment: Distal myopathy is a common feature reported in affected cases.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.4 MRUPAV Bryony Thompson Marked STR: MRUPAV as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.4 MRUPAV Bryony Thompson Str: mrupav has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.4 MRUPAV Bryony Thompson Classified STR: MRUPAV as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.4 MRUPAV Bryony Thompson Str: mrupav has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.3 MRUPAV Bryony Thompson STR: MRUPAV was added
STR: MRUPAV was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for STR: MRUPAV was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: MRUPAV were set to 32451610; 37145156; 36151849; 35499779
Phenotypes for STR: MRUPAV were set to myopathy, distal, with rimmed vacuoles MONDO:0014945
Review for STR: MRUPAV was set to GREEN
STR: MRUPAV was marked as clinically relevant
Added comment: Expansion of 33-mer (33 amino acids, 99 bp) identified in coding exon 3 (exon 5) of PLIN4 via linkage analysis and long read sequencing in a large Italian cohort with progressive myopathy with specific pathology including rimmed ubiquitin-positive autophagic vacuolation.
Suggested disease name myopathy with rimmed ubiquitin-positive autophagic vacuolation (MRUPAV)
An additional 4 unrelated Chinese families/probands were reported.
Normal PLIN4 alleles: 27-31 x 33-mer
Pathogenic: ≥39 x 33-mer
Sources: Literature
Repeat Disorders v0.155 MRUPAV Bryony Thompson Marked STR: MRUPAV as ready
Repeat Disorders v0.155 MRUPAV Bryony Thompson Str: mrupav has been classified as Green List (High Evidence).
Repeat Disorders v0.155 MRUPAV Bryony Thompson Classified STR: MRUPAV as Green List (high evidence)
Repeat Disorders v0.155 MRUPAV Bryony Thompson Str: mrupav has been classified as Green List (High Evidence).
Repeat Disorders v0.154 MRUPAV Bryony Thompson STR: MRUPAV was added
STR: MRUPAV was added to Repeat Disorders. Sources: Literature
adult-onset tags were added to STR: MRUPAV.
Mode of inheritance for STR: MRUPAV was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: MRUPAV were set to 32451610; 37145156; 36151849; 35499779
Phenotypes for STR: MRUPAV were set to myopathy, distal, with rimmed vacuoles MONDO:0014945
Review for STR: MRUPAV was set to GREEN
STR: MRUPAV was marked as clinically relevant
Added comment: Expansion of 33-mer (33 amino acids, 99 bp) identified in coding exon 3 (exon 5) of PLIN4 via linkage analysis and long read sequencing in a large Italian cohort with progressive myopathy with specific pathology including rimmed ubiquitin-positive autophagic vacuolation.
Suggested disease name myopathy with rimmed ubiquitin-positive autophagic vacuolation (MRUPAV)
An additional 4 unrelated Chinese families/probands were reported.
Normal PLIN4 alleles: 27-31 x 33-mer
Pathogenic: ≥39 x 33-mer
Sources: Literature
Congenital Heart Defect v0.288 ZMYND10 Bryony Thompson Marked gene: ZMYND10 as ready
Congenital Heart Defect v0.288 ZMYND10 Bryony Thompson Gene: zmynd10 has been classified as Green List (High Evidence).
Cerebral Palsy v1.86 IFIH1 Luisa Weiss gene: IFIH1 was added
gene: IFIH1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: IFIH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFIH1 were set to 34788679; 33177673; 33528536
Phenotypes for gene: IFIH1 were set to Aicardi-Goutieres syndrome 7 MIM#615846; Immunodeficiency 95 MIM#619773; Singleton-Merten syndrome MIM#182250
Review for gene: IFIH1 was set to GREEN
Added comment: Three large CP cohort publication with one patient each presenting with CP and harbouring a IFIH1 mutation (missense mutations). Note that the gene can have a very variable phenotype and incomplete penetrance has been reported for other diseases associated with mutatons in this gene.
Sources: Literature
Congenital Heart Defect v0.288 ZMYND10 Bryony Thompson Classified gene: ZMYND10 as Green List (high evidence)
Congenital Heart Defect v0.288 ZMYND10 Bryony Thompson Gene: zmynd10 has been classified as Green List (High Evidence).
Cerebral Palsy v1.86 HUWE1 Luisa Weiss gene: HUWE1 was added
gene: HUWE1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: HUWE1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: HUWE1 were set to 31700678
Phenotypes for gene: HUWE1 were set to Intellectual developmental disorder, X-linked syndromic, Turner type MIM#309590
Review for gene: HUWE1 was set to AMBER
Added comment: 1 large CP cohort study with three cases of HUWE1 mutation, two of which are VUS and one a likely benign variant. Note that one of the VUS is paternally inherited. No certain phenotypic overlap as HUWE1 mutations tend to cause ID, sometimes with muscular hypotonia.
Sources: Literature
Congenital Heart Defect v0.287 ZMYND10 Bryony Thompson gene: ZMYND10 was added
gene: ZMYND10 was added to Congenital Heart Defect. Sources: Other
Mode of inheritance for gene: ZMYND10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZMYND10 were set to 23891471; 23891469; 29402277
Phenotypes for gene: ZMYND10 were set to Primary ciliary dyskinesia 22 MONDO:0014192
Review for gene: ZMYND10 was set to GREEN
gene: ZMYND10 was marked as current diagnostic
Added comment: CHD is a commonly reported feature of the condition.
Sources: Other
Cerebral Palsy v1.86 HPRT1 Luisa Weiss gene: HPRT1 was added
gene: HPRT1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: HPRT1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: HPRT1 were set to 34788679, 30799092
Phenotypes for gene: HPRT1 were set to Hyperuricemia, HRPT-related MIM#300323; Lesch-Nyhan syndrome MIM#300322
Review for gene: HPRT1 was set to GREEN
Added comment: Several (>3) cases in large CP cohort studies present with different forms of CP.
Sources: Literature
Congenital Heart Defect v0.286 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Congenital Heart Defect v0.285 TTC25 Bryony Thompson Marked gene: TTC25 as ready
Congenital Heart Defect v0.285 TTC25 Bryony Thompson Gene: ttc25 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.285 TTC25 Bryony Thompson Classified gene: TTC25 as Green List (high evidence)
Congenital Heart Defect v0.285 TTC25 Bryony Thompson Gene: ttc25 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.284 TTC25 Bryony Thompson gene: TTC25 was added
gene: TTC25 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: TTC25 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC25 were set to 34215651; 33746037; 27486780
Phenotypes for gene: TTC25 were set to primary ciliary dyskinesia 35 MONDO:0014910
Review for gene: TTC25 was set to GREEN
Added comment: At least 3 probands reported with congenital heart defects and a supporting mouse model.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.2 MB Bryony Thompson Marked gene: MB as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.2 MB Bryony Thompson Gene: mb has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.2 MB Bryony Thompson Classified gene: MB as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.2 MB Bryony Thompson Gene: mb has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.1 MB Bryony Thompson gene: MB was added
gene: MB was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Other
Mode of inheritance for gene: MB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MB were set to 35527200; 30918256
Phenotypes for gene: MB were set to Myopathy, sarcoplasmic body MIM#620286
Review for gene: MB was set to GREEN
Added comment: Single recurrent variant (H98Y) was reported in multiple unrelated families. Only reported pathogenic variant to date.
Sources: Other
Myopathy Superpanel v4.1 Bryony Thompson Changed child panels to: Malignant Hyperthermia Susceptibility; Skeletal Muscle Channelopathies; Rhabdomyolysis and Metabolic Myopathy; Muscular dystrophy and myopathy_Paediatric; Limb-Girdle Muscular Dystrophy and Distal Myopathy
Rhabdomyolysis and Metabolic Myopathy v1.0 Bryony Thompson promoted panel to version 1.0
Muscular dystrophy and myopathy_Paediatric v1.0 Bryony Thompson promoted panel to version 1.0
Muscular dystrophy and myopathy_Paediatric v0.202 Bryony Thompson Panel name changed from Muscular dystrophy_Paediatric to Muscular dystrophy and myopathy_Paediatric
HPO terms changed from Muscular dystrophy, HP:0003560; Elevated circulating creatine kinase concentration, HP:0003236 to Muscular dystrophy, HP:0003560; Elevated circulating creatine kinase concentration, HP:0003236; Myopathy, HP:0003198
List of related panels changed from Muscular dystrophy; HP:0003560; Elevated circulating creatine kinase concentration; HP:0003236 to Muscular dystrophy; HP:0003560; Elevated circulating creatine kinase concentration; HP:0003236; Myopathy; HP:0003198
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.0 Bryony Thompson promoted panel to version 1.0
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.156 VCP Bryony Thompson Classified gene: VCP as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.156 VCP Bryony Thompson Added comment: Comment on list classification: Definitive gene-disease validity - reviewed 23/12/2021
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.156 VCP Bryony Thompson Gene: vcp has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.200 TRDN Bryony Thompson Marked gene: TRDN as ready
Muscular dystrophy and myopathy_Paediatric v0.200 TRDN Bryony Thompson Gene: trdn has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.200 TRDN Bryony Thompson Classified gene: TRDN as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.200 TRDN Bryony Thompson Added comment: Comment on list classification: Congenital myopathy can be a feature of the condition
Muscular dystrophy and myopathy_Paediatric v0.200 TRDN Bryony Thompson Gene: trdn has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.199 TRDN Bryony Thompson gene: TRDN was added
gene: TRDN was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: TRDN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRDN were set to 28202702; 30649896; 34415104
Phenotypes for gene: TRDN were set to Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness, MIM# 615441
Muscular dystrophy and myopathy_Paediatric v0.198 TNNT3 Bryony Thompson Marked gene: TNNT3 as ready
Muscular dystrophy and myopathy_Paediatric v0.198 TNNT3 Bryony Thompson Gene: tnnt3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.198 TNNT3 Bryony Thompson Classified gene: TNNT3 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.198 TNNT3 Bryony Thompson Gene: tnnt3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.197 TNNT3 Bryony Thompson gene: TNNT3 was added
gene: TNNT3 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: TNNT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNNT3 were set to 33977145; 29266598; 23775847
Phenotypes for gene: TNNT3 were set to Nemaline myopathy MONDO:0018958
Review for gene: TNNT3 was set to GREEN
Added comment: 2 unrelated families with nemaline myopathy and splice variants. Also, a supporting mouse model.
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.196 TNNT1 Bryony Thompson Marked gene: TNNT1 as ready
Muscular dystrophy and myopathy_Paediatric v0.196 TNNT1 Bryony Thompson Gene: tnnt1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.196 TNNT1 Bryony Thompson Classified gene: TNNT1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.196 TNNT1 Bryony Thompson Added comment: Comment on list classification: Biallelic Nemaline myopathy is classified as definitive by ClinGen Congenital Myopathies VCEP (reviewed 07/05/2020) with a LoF mechanism of disease, whereas monoallelic Nemaline myopathy is classified as limited (reviewed 22/06/2020) with an expected GoF mechanism of disease.
Muscular dystrophy and myopathy_Paediatric v0.196 TNNT1 Bryony Thompson Gene: tnnt1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.195 TNNT1 Bryony Thompson gene: TNNT1 was added
gene: TNNT1 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: TNNT1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TNNT1 were set to 10952871; 32994279; 32819427; 31970803; 31604653; 29931346; 29178646
Phenotypes for gene: TNNT1 were set to Nemaline myopathy 5 MONDO:0011539; Nemaline myopathy MONDO:0018958
Rhabdomyolysis and Metabolic Myopathy v0.192 TAMM41 Bryony Thompson Marked gene: TAMM41 as ready
Rhabdomyolysis and Metabolic Myopathy v0.192 TAMM41 Bryony Thompson Gene: tamm41 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.192 TAMM41 Bryony Thompson Classified gene: TAMM41 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.192 TAMM41 Bryony Thompson Gene: tamm41 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.191 TAMM41 Bryony Thompson gene: TAMM41 was added
gene: TAMM41 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Other
Mode of inheritance for gene: TAMM41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAMM41 were set to 35321494; 29253589
Phenotypes for gene: TAMM41 were set to Combined oxidative phosphorylation deficiency-56 (COXPD56), MIM#620139
Rhabdomyolysis and Metabolic Myopathy v0.190 SUCLG1 Bryony Thompson Marked gene: SUCLG1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.190 SUCLG1 Bryony Thompson Gene: suclg1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.190 SUCLG1 Bryony Thompson Classified gene: SUCLG1 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.190 SUCLG1 Bryony Thompson Gene: suclg1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.189 SUCLG1 Bryony Thompson gene: SUCLG1 was added
gene: SUCLG1 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Other
Mode of inheritance for gene: SUCLG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUCLG1 were set to 30560055; 29217198
Phenotypes for gene: SUCLG1 were set to mitochondrial DNA depletion syndrome 9 MONDO:0009504
Rhabdomyolysis and Metabolic Myopathy v0.188 SCO2 Bryony Thompson Marked gene: SCO2 as ready
Rhabdomyolysis and Metabolic Myopathy v0.188 SCO2 Bryony Thompson Gene: sco2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.188 SCO2 Bryony Thompson Classified gene: SCO2 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.188 SCO2 Bryony Thompson Gene: sco2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.187 SCO2 Bryony Thompson gene: SCO2 was added
gene: SCO2 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Other
Mode of inheritance for gene: SCO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCO2 were set to 23719228
Phenotypes for gene: SCO2 were set to cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 MONDO:0011451
gene: SCO2 was marked as current diagnostic
Rhabdomyolysis and Metabolic Myopathy v0.186 RMND1 Bryony Thompson Classified gene: RMND1 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.186 RMND1 Bryony Thompson Gene: rmnd1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.185 RMND1 Bryony Thompson gene: RMND1 was added
gene: RMND1 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Other
Mode of inheritance for gene: RMND1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RMND1 were set to 23022099; 25604853; 27843092
Phenotypes for gene: RMND1 were set to Combined oxidative phosphorylation defect type 11 MONDO:0013969
Cerebral Palsy v1.86 HPDL Luisa Weiss reviewed gene: HPDL: Rating: GREEN; Mode of pathogenicity: None; Publications: 33634263, 32707086; Phenotypes: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities MIM#619026; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and Metabolic Myopathy v0.184 TSFM Bryony Thompson Classified gene: TSFM as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.184 TSFM Bryony Thompson Gene: tsfm has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.183 TSFM Bryony Thompson Deleted their review
Rhabdomyolysis and Metabolic Myopathy v0.183 TSFM Bryony Thompson commented on gene: TSFM
Rhabdomyolysis and Metabolic Myopathy v0.183 TSFM Bryony Thompson Deleted their review
Muscular dystrophy and myopathy_Paediatric v0.194 PYROXD1 Bryony Thompson Marked gene: PYROXD1 as ready
Muscular dystrophy and myopathy_Paediatric v0.194 PYROXD1 Bryony Thompson Gene: pyroxd1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.194 PYROXD1 Bryony Thompson Classified gene: PYROXD1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.194 PYROXD1 Bryony Thompson Added comment: Comment on list classification: Definitive gene-disease validity classification by ClinGen Congenital Myopathy VCEP - reviewed 05/11/2019
Muscular dystrophy and myopathy_Paediatric v0.194 PYROXD1 Bryony Thompson Gene: pyroxd1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.193 PYROXD1 Bryony Thompson gene: PYROXD1 was added
gene: PYROXD1 was added to Muscular dystrophy_Paediatric. Sources: Expert list
Mode of inheritance for gene: PYROXD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYROXD1 were set to 30345904; 30515627; 27745833
Phenotypes for gene: PYROXD1 were set to Myofibrillar myopathy 8 MONDO:0014993
gene: PYROXD1 was marked as current diagnostic
Muscular dystrophy and myopathy_Paediatric v0.192 MYO18B Bryony Thompson Marked gene: MYO18B as ready
Muscular dystrophy and myopathy_Paediatric v0.192 MYO18B Bryony Thompson Gene: myo18b has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.192 MYO18B Bryony Thompson Classified gene: MYO18B as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.192 MYO18B Bryony Thompson Added comment: Comment on list classification: Moderate gene-disease validity classified by ClinGen Congenital Myopathy VCEP - reviewed 28/06/2021
Muscular dystrophy and myopathy_Paediatric v0.192 MYO18B Bryony Thompson Gene: myo18b has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.191 MYO18B Bryony Thompson gene: MYO18B was added
gene: MYO18B was added to Muscular dystrophy_Paediatric. Sources: Expert list
Mode of inheritance for gene: MYO18B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYO18B were set to 25748484; 27858739; 32637634; 32184166; 27879346
Phenotypes for gene: MYO18B were set to Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome MONDO:0014689
Mendeliome v1.937 MYMX Bryony Thompson Marked gene: MYMX as ready
Mendeliome v1.937 MYMX Bryony Thompson Gene: mymx has been classified as Amber List (Moderate Evidence).
Mendeliome v1.937 MYMX Bryony Thompson Classified gene: MYMX as Amber List (moderate evidence)
Mendeliome v1.937 MYMX Bryony Thompson Gene: mymx has been classified as Amber List (Moderate Evidence).
Mendeliome v1.936 MYMX Bryony Thompson gene: MYMX was added
gene: MYMX was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYMX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYMX were set to 35642635
Phenotypes for gene: MYMX were set to Carey-Fineman-Ziter syndrome MONDO:0009700
Review for gene: MYMX was set to AMBER
Added comment: Single family, two siblings with weakness of the facial musculature, hypomimic face, increased overbite, micrognathia, and facial dysmorphism with homozygous p.Arg46*. The phenotype resembles CFZ syndrome. The variant prevents fusion of myoblasts from patient-derived iPSCs. Mouse model recapitulates a lethal CFZS-like phenotype.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v0.190 MYMX Bryony Thompson Marked gene: MYMX as ready
Muscular dystrophy and myopathy_Paediatric v0.190 MYMX Bryony Thompson Gene: mymx has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.190 MYMX Bryony Thompson Classified gene: MYMX as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v0.190 MYMX Bryony Thompson Gene: mymx has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.189 MYMX Bryony Thompson gene: MYMX was added
gene: MYMX was added to Muscular dystrophy_Paediatric. Sources: Literature
Mode of inheritance for gene: MYMX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYMX were set to 35642635
Phenotypes for gene: MYMX were set to Carey-Fineman-Ziter syndrome MONDO:0009700
Review for gene: MYMX was set to AMBER
Added comment: Single family, two siblings with weakness of the facial musculature, hypomimic face, increased overbite, micrognathia, and facial dysmorphism with homozygous p.Arg46*. The phenotype resembles CFZ syndrome. The variant prevents fusion of myoblasts from patient-derived iPSCs. Mouse model recapitulates a lethal CFZS-like phenotype.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v0.188 MYMK Bryony Thompson Classified gene: MYMK as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.188 MYMK Bryony Thompson Gene: mymk has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.187 MYMK Bryony Thompson Classified gene: MYMK as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.187 MYMK Bryony Thompson Gene: mymk has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.186 MYMK Bryony Thompson Marked gene: MYMK as ready
Muscular dystrophy and myopathy_Paediatric v0.186 MYMK Bryony Thompson Gene: mymk has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.186 MYMK Bryony Thompson gene: MYMK was added
gene: MYMK was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: MYMK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYMK were set to 32333597; 30065953
Phenotypes for gene: MYMK were set to Carey-Fineman-Ziter syndrome MONDO:0009700
Review for gene: MYMK was set to GREEN
gene: MYMK was marked as current diagnostic
Added comment: Carey-Fineman-Ziter syndrome is considered a congenital myopathy
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.185 MYH2 Bryony Thompson Marked gene: MYH2 as ready
Muscular dystrophy and myopathy_Paediatric v0.185 MYH2 Bryony Thompson Gene: myh2 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.185 MYH2 Bryony Thompson Classified gene: MYH2 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.185 MYH2 Bryony Thompson Added comment: Comment on list classification: Definitive gene-disease validity by the ClinGen Congenital Myopathy VCEP - reviewed 09/03/2020
Muscular dystrophy and myopathy_Paediatric v0.185 MYH2 Bryony Thompson Gene: myh2 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.184 MYH2 Bryony Thompson gene: MYH2 was added
gene: MYH2 was added to Muscular dystrophy_Paediatric. Sources: Expert list
Mode of inheritance for gene: MYH2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: MYH2 were set to 20418530; 15548556; 24193343; 11114175; 23489661; 32578970; 29934118; 28729039; 27490141; 27177998
Phenotypes for gene: MYH2 were set to Myopathy, proximal, and ophthalmoplegia MONDO:0011577
gene: MYH2 was marked as current diagnostic
Cerebral Palsy v1.86 GRIN1 Luisa Weiss gene: GRIN1 was added
gene: GRIN1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GRIN1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GRIN1 were set to 33528536; 34788679
Phenotypes for gene: GRIN1 were set to Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant MIM#614254 AD
Review for gene: GRIN1 was set to GREEN
Added comment: 3 individuals in a large CP cohort study with heterozygous mutations in GRIN1, two of which reported to be de novo. Another single patient in a large cohort study with heterozygous de novo mutation. All of these mutations are missense mutations. Note that there are other disorders associated with this gene that are due to biallelic mutations in GRIN1, however, for CP only heterozygous mutations are described so far.
Sources: Literature
Cerebral Palsy v1.86 GCDH Luisa Weiss Deleted their comment
Cerebral Palsy v1.86 GCDH Luisa Weiss edited their review of gene: GCDH: Added comment: One larger cohort study on 34 patients with Glutaric Aciduria Type 1 (GA1) that showed that patient diagnosed clinically will develop a CP at school age in 64% (7 out of 11 cases).
In addition, there are several case reports of patients with dystonic, dyskinetic or spastic CP that were diagnosed with biallelic mutations in GCDH and biochemically corresponding features. Also, one case in a larger cohort study of patients with atypical CP (no mutation information given for this patient).; Changed rating: GREEN; Changed publications: 30542205, 26593172, 25280894, 30271473, 35822093
Cerebral Palsy v1.86 COL4A1 Luisa Weiss changed review comment from: More than 8 individuals reported with heterozygous mutations in COL4A2 and CP in large cohort studies. Note that some of these mutations have been inherited from one parent so incomplete penetrance is likely. In one study, it is hypothesized that COL4A2 mutations can cause vascular instability and might thus pose a risk for perinatal intracranial hemorrhage resulting in CP.; to: More than 8 individuals reported with heterozygous mutations in COL4A1 and CP in large cohort studies. Note that some of these mutations have been inherited from one parent so incomplete penetrance is likely. In one study, it is hypothesized that COL4A1 mutations can cause vascular instability and might thus pose a risk for perinatal intracranial hemorrhage resulting in CP.
Mendeliome v1.935 NOP10 Zornitza Stark Phenotypes for gene: NOP10 were changed from Dyskeratosis congenita, autosomal recessive 1, MIM#224230; Telomere syndrome MONDO:0100137 to Dyskeratosis congenita, autosomal recessive 1, MIM#224230; Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9, MIM# 620400
Mendeliome v1.934 NOP10 Zornitza Stark Publications for gene: NOP10 were set to 17507419; 32554502
Mendeliome v1.933 NOP10 Zornitza Stark Mode of inheritance for gene: NOP10 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.932 NOP10 Zornitza Stark edited their review of gene: NOP10: Added comment: PMID 32139460: large multiplex family with 4 affected individuals segregating a heterozygous variant.; Changed rating: AMBER; Changed publications: 17507419, 32139460; Changed phenotypes: Dyskeratosis congenita, autosomal recessive 1, MIM#224230, Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9, MIM# 620400; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bone Marrow Failure v1.44 NOP10 Zornitza Stark Phenotypes for gene: NOP10 were changed from Dyskeratosis congenita, autosomal recessive 1, MIM#224230 to Dyskeratosis congenita, autosomal recessive 1, MIM#224230; Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9, MIM# 620400
Bone Marrow Failure v1.43 NOP10 Zornitza Stark Publications for gene: NOP10 were set to 17507419
Bone Marrow Failure v1.42 NOP10 Zornitza Stark Mode of inheritance for gene: NOP10 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bone Marrow Failure v1.41 NOP10 Zornitza Stark edited their review of gene: NOP10: Added comment: PMID 32139460: multiplex family with 4 affected individuals and heterozygous variant in NOP10.; Changed rating: AMBER; Changed publications: 17507419, 32139460; Changed phenotypes: Dyskeratosis congenita, autosomal recessive 1, MIM#224230, Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9, MIM# 620400; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.932 MFN2 Zornitza Stark Phenotypes for gene: MFN2 were changed from Charcot-Marie-Tooth disease, axonal, type 2A2A, OMIM #609260; Charcot-Marie-Tooth disease, axonal, type 2A2B, OMIM #617087; Hereditary motor and sensory neuropathy VIA, OMIM #601152 to Charcot-Marie-Tooth disease, axonal, type 2A2A 609260; Charcot-Marie-Tooth disease, axonal, type 2A2B, MIM# 617087; Hereditary motor and sensory neuropathy VIA, MIM# 601152; Lipomatosis, multiple symmetric, with or without peripheral neuropathy, MIM# 151800
Mendeliome v1.931 MFN2 Zornitza Stark edited their review of gene: MFN2: Changed phenotypes: Charcot-Marie-Tooth disease, axonal, type 2A2A 609260, Charcot-Marie-Tooth disease, axonal, type 2A2B, MIM# 617087, Hereditary motor and sensory neuropathy VIA, MIM# 601152, Lipomatosis, multiple symmetric, with or without peripheral neuropathy, MIM# 151800
Hereditary Neuropathy - complex v0.166 DARS2 Sangavi Sivagnanasundram reviewed gene: DARS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 20506600, 19592391, 33574740; Phenotypes: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) (MIM#611105); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.183 MEGF10 Bryony Thompson Marked gene: MEGF10 as ready
Muscular dystrophy and myopathy_Paediatric v0.183 MEGF10 Bryony Thompson Gene: megf10 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.183 MEGF10 Bryony Thompson Classified gene: MEGF10 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.183 MEGF10 Bryony Thompson Gene: megf10 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.182 MEGF10 Bryony Thompson gene: MEGF10 was added
gene: MEGF10 was added to Muscular dystrophy_Paediatric. Sources: Expert list
Mode of inheritance for gene: MEGF10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MEGF10 were set to 22101682; 22371254; 23453856; 27460346
Phenotypes for gene: MEGF10 were set to MEGF10-Related Myopathy MONDO:0013731
gene: MEGF10 was marked as current diagnostic
Added comment: Assigned a definitive gene-disease validity classification by the ClinGen congenital myopathy GCEP - 27/1/2020
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.183 MAN2B1 Bryony Thompson Marked gene: MAN2B1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.183 MAN2B1 Bryony Thompson Gene: man2b1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.183 MAN2B1 Bryony Thompson Classified gene: MAN2B1 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.183 MAN2B1 Bryony Thompson Gene: man2b1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.182 MAN2B1 Bryony Thompson gene: MAN2B1 was added
gene: MAN2B1 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert list
Mode of inheritance for gene: MAN2B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2B1 were set to 20301570
Phenotypes for gene: MAN2B1 were set to Alpha-mannosidosis MONDO:0009561
Review for gene: MAN2B1 was set to GREEN
gene: MAN2B1 was marked as current diagnostic
Added comment: Metabolic myopathy is a well-established feature of the condition.
Sources: Expert list
Muscular dystrophy and myopathy_Paediatric v0.181 FKTN Bryony Thompson Marked gene: FKTN as ready
Muscular dystrophy and myopathy_Paediatric v0.181 FKTN Bryony Thompson Gene: fktn has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.181 FKTN Bryony Thompson Phenotypes for gene: FKTN were changed from to Muscular dystrophy-dystroglycanopathy MONDO:0018276
Muscular dystrophy and myopathy_Paediatric v0.180 FKTN Bryony Thompson Publications for gene: FKTN were set to
Muscular dystrophy and myopathy_Paediatric v0.179 FKTN Bryony Thompson Mode of inheritance for gene: FKTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.178 FKBP14 Bryony Thompson Marked gene: FKBP14 as ready
Muscular dystrophy and myopathy_Paediatric v0.178 FKBP14 Bryony Thompson Gene: fkbp14 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.178 FKBP14 Bryony Thompson Classified gene: FKBP14 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.178 FKBP14 Bryony Thompson Gene: fkbp14 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.177 FKBP14 Bryony Thompson gene: FKBP14 was added
gene: FKBP14 was added to Muscular dystrophy_Paediatric. Sources: Literature
Mode of inheritance for gene: FKBP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKBP14 were set to 31132235
Phenotypes for gene: FKBP14 were set to Ehlers-Danlos syndrome, kyphoscoliotic and deafness type MONDO:0013800
Review for gene: FKBP14 was set to GREEN
gene: FKBP14 was marked as current diagnostic
Added comment: Affected individuals typically present at birth with congenital hypotonia and weakness.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v0.176 FAM111B Bryony Thompson Marked gene: FAM111B as ready
Muscular dystrophy and myopathy_Paediatric v0.176 FAM111B Bryony Thompson Gene: fam111b has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.176 FAM111B Bryony Thompson Classified gene: FAM111B as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.176 FAM111B Bryony Thompson Gene: fam111b has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.175 FAM111B Bryony Thompson gene: FAM111B was added
gene: FAM111B was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: FAM111B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FAM111B were set to 27748098
Phenotypes for gene: FAM111B were set to Hereditary sclerosing poikiloderma with tendon and pulmonary involvement MONDO:0014310
Mode of pathogenicity for gene: FAM111B was set to Other
Review for gene: FAM111B was set to GREEN
Added comment: Muscle contractures are usually seen in childhood. The majority of affected individuals develop progressive weakness of the proximal and distal muscles of all four limbs, beginning with the proximal muscles. Serum creatine kinase is either normal or slightly increased and electromyography may show a normal or myopathic pattern. The mechanism of disease is unknown, but based on the spectrum of pathogenic variants it is expected to be dominant-negative.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5246 RHOBTB2 Zornitza Stark Publications for gene: RHOBTB2 were set to 29768694; 29276004
Intellectual disability syndromic and non-syndromic v0.5245 RHOBTB2 Zornitza Stark Mode of inheritance for gene: RHOBTB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5244 RHOBTB2 Zornitza Stark edited their review of gene: RHOBTB2: Added comment: PMID 37165955: 16 individuals with de novo heterozygous missense variants in the BTB domain region and a severe DEE as previously reported. In addition, 6 individuals with de novo missense variants in the GTPase domain and a more variable neurodevelopmental phenotypes with or without epilepsy. In contrast to variants in the BTB domain region, variants in the GTPase domain do not impair proteasomal degradation of RHOBTB2 in vitro, indicating different functional consequences.
In addition, 9 families with observed bi-allelic splice-site and truncating variants with variable neurodevelopmental phenotypes, indicating that complete loss of RHOBTB2 is pathogenic as well.; Changed publications: 29768694, 29276004, 37165955; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1864 RHOBTB2 Zornitza Stark Publications for gene: RHOBTB2 were set to 29768694; 29276004
Genetic Epilepsy v0.1863 RHOBTB2 Zornitza Stark Mode of inheritance for gene: RHOBTB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1862 RHOBTB2 Zornitza Stark edited their review of gene: RHOBTB2: Added comment: PMID 37165955: 16 individuals with de novo heterozygous missense variants in the BTB domain region and a severe DEE as previously reported. In addition, 6 individuals with de novo missense variants in the GTPase domain and a more variable neurodevelopmental phenotypes with or without epilepsy. In contrast to variants in the BTB domain region, variants in the GTPase domain do not impair proteasomal degradation of RHOBTB2 in vitro, indicating different functional consequences.
In addition, 9 families with observed bi-allelic splice-site and truncating variants with variable neurodevelopmental phenotypes, indicating that complete loss of RHOBTB2 is pathogenic as well.; Changed publications: 29768694, 29276004, 37165955; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.931 RHOBTB2 Zornitza Stark Publications for gene: RHOBTB2 were set to 29276004; 29768694
Mendeliome v1.930 RHOBTB2 Zornitza Stark Mode of pathogenicity for gene: RHOBTB2 was changed from Other to None
Mendeliome v1.929 RHOBTB2 Zornitza Stark Mode of inheritance for gene: RHOBTB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.928 RHOBTB2 Zornitza Stark reviewed gene: RHOBTB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37165955; Phenotypes: Epileptic encephalopathy, early infantile, 64, MIM#618004; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.154 DM1 Bryony Thompson Marked STR: DM1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.154 DM1 Bryony Thompson Str: dm1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.154 DM1 Bryony Thompson Classified STR: DM1 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.154 DM1 Bryony Thompson Str: dm1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.153 DM1 Bryony Thompson STR: DM1 was added
STR: DM1 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Expert list
Mode of inheritance for STR: DM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: DM1 were set to 20301344; 29325606
Phenotypes for STR: DM1 were set to Myotonic dystrophy 1 MIM#160900
Review for STR: DM1 was set to GREEN
STR: DM1 was marked as clinically relevant
Added comment: HGVS nomenclature: NM_001081560.2:c.*224_*226CTG[X]
RNA toxic gain of function is mechanism of disease
Premutation: 35-49 repeats, no clinical signs
Mild: 50-~150 repeats, age of onset 20-70 yrs, clinical signs - cataracts, mild myotonia
Classic: ~100-~1,000 repeats, age of onset 10-30 yrs, clinical signs - weakness, myotonia, cataracts, balding, cardiac arrhythmia
Congenital: >1,000 repeats, age of onset birth-10 yrs , clinical signs - infantile hypotonia, respiratory deficits, intellectual disability, classic signs in adults
Sources: Expert list
Hereditary Neuropathy - complex v0.166 CLP1 Sangavi Sivagnanasundram reviewed gene: CLP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24766809, 24766810; Phenotypes: Pontocerebellar hypoplasia, type 10 (MIM#615803); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.152 CHKB Bryony Thompson Marked gene: CHKB as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.152 CHKB Bryony Thompson Gene: chkb has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.152 CHKB Bryony Thompson Classified gene: CHKB as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.152 CHKB Bryony Thompson Gene: chkb has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.151 CHKB Bryony Thompson gene: CHKB was added
gene: CHKB was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for gene: CHKB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHKB were set to 37011121
Phenotypes for gene: CHKB were set to megaconial type congenital muscular dystrophy MONDO:0011246; CHKB-Related Muscular Dystrophy
Review for gene: CHKB was set to AMBER
Added comment: 3/47 affected individuals have been diagnosed with adolescent-onset limb-girdle muscular dystrophy. 2 presented with rhabdomyolysis. 1 had mild intellectual disability. Behaviour abnormalities and dilated cardiomyopathy were not observed.
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v0.181 CHKB Bryony Thompson Phenotypes for gene: CHKB were changed from Muscular dystrophy, congenital, megaconial type MIM#602541 to megaconial type congenital muscular dystrophy MONDO:0011246; recurrent rhabdomyolysis; CHKB-Related Muscular Dystrophy
Rhabdomyolysis and Metabolic Myopathy v0.180 CHKB Bryony Thompson Publications for gene: CHKB were set to 26782016
Rhabdomyolysis and Metabolic Myopathy v0.179 CHKB Bryony Thompson Classified gene: CHKB as Amber List (moderate evidence)
Rhabdomyolysis and Metabolic Myopathy v0.179 CHKB Bryony Thompson Gene: chkb has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.178 CHKB Bryony Thompson reviewed gene: CHKB: Rating: AMBER; Mode of pathogenicity: None; Publications: 37011121; Phenotypes: megaconial type congenital muscular dystrophy MONDO:0011246, recurrent rhabdomyolysis, CHKB-Related Muscular Dystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and Metabolic Myopathy v0.178 CHKB Bryony Thompson Deleted their review
Rhabdomyolysis and Metabolic Myopathy v0.178 AHCY Bryony Thompson Deleted their review
Rhabdomyolysis and Metabolic Myopathy v0.178 AHCY Bryony Thompson Publications for gene: AHCY were set to 28779239
Rhabdomyolysis and Metabolic Myopathy v0.177 AHCY Bryony Thompson Classified gene: AHCY as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.177 AHCY Bryony Thompson Gene: ahcy has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.176 AHCY Bryony Thompson commented on gene: AHCY
Rhabdomyolysis and Metabolic Myopathy v0.176 AHCY Bryony Thompson Deleted their review
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.150 UNC45B Bryony Thompson Marked gene: UNC45B as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.150 UNC45B Bryony Thompson Gene: unc45b has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.150 UNC45B Bryony Thompson Classified gene: UNC45B as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.150 UNC45B Bryony Thompson Gene: unc45b has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.149 SVIL Bryony Thompson Marked gene: SVIL as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.149 SVIL Bryony Thompson Gene: svil has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.149 SVIL Bryony Thompson Classified gene: SVIL as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.149 SVIL Bryony Thompson Gene: svil has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.148 MYL2 Bryony Thompson Marked gene: MYL2 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.148 MYL2 Bryony Thompson Gene: myl2 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.148 MYL2 Bryony Thompson Classified gene: MYL2 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.148 MYL2 Bryony Thompson Gene: myl2 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.147 KY Bryony Thompson Marked gene: KY as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.147 KY Bryony Thompson Gene: ky has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.147 KY Bryony Thompson Classified gene: KY as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.147 KY Bryony Thompson Gene: ky has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.176 GFER Bryony Thompson Marked gene: GFER as ready
Rhabdomyolysis and Metabolic Myopathy v0.176 GFER Bryony Thompson Gene: gfer has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.176 GFER Bryony Thompson Classified gene: GFER as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.176 GFER Bryony Thompson Gene: gfer has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.175 FASTKD2 Bryony Thompson Marked gene: FASTKD2 as ready
Rhabdomyolysis and Metabolic Myopathy v0.175 FASTKD2 Bryony Thompson Gene: fastkd2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.175 FASTKD2 Bryony Thompson Classified gene: FASTKD2 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.175 FASTKD2 Bryony Thompson Gene: fastkd2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.174 AIFM1 Bryony Thompson Marked gene: AIFM1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.174 AIFM1 Bryony Thompson Gene: aifm1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.174 AIFM1 Bryony Thompson Classified gene: AIFM1 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.174 AIFM1 Bryony Thompson Gene: aifm1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.173 AIFM1 Bryony Thompson Mode of inheritance for gene: AIFM1 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Rhabdomyolysis and Metabolic Myopathy v0.172 AIFM1 Sangavi Sivagnanasundram edited their review of gene: AIFM1: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Rhabdomyolysis and Metabolic Myopathy v0.172 AGK Bryony Thompson Marked gene: AGK as ready
Rhabdomyolysis and Metabolic Myopathy v0.172 AGK Bryony Thompson Gene: agk has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.172 AGK Bryony Thompson Classified gene: AGK as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.172 AGK Bryony Thompson Gene: agk has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.171 AARS2 Bryony Thompson Marked gene: AARS2 as ready
Rhabdomyolysis and Metabolic Myopathy v0.171 AARS2 Bryony Thompson Gene: aars2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.171 AARS2 Bryony Thompson Classified gene: AARS2 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.171 AARS2 Bryony Thompson Gene: aars2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.170 ABHD5 Bryony Thompson Marked gene: ABHD5 as ready
Rhabdomyolysis and Metabolic Myopathy v0.170 ABHD5 Bryony Thompson Gene: abhd5 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.170 ABHD5 Bryony Thompson Classified gene: ABHD5 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.170 ABHD5 Bryony Thompson Gene: abhd5 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.169 ABHD5 Bryony Thompson gene: ABHD5 was added
gene: ABHD5 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Expert list
Mode of inheritance for gene: ABHD5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD5 were set to 31883530
Phenotypes for gene: ABHD5 were set to Dorfman-Chanarin disease MONDO:0010155
Review for gene: ABHD5 was set to GREEN
gene: ABHD5 was marked as current diagnostic
Added comment: A disorder of glycerolipid metabolism. Myopathy, identified through raised CK levels and muscle biopsy, was a commonly observed finding in 59% (86/147) cases with ABHD5 deficiency. The myopathy tends to generally be a slowly progressive muscle weakness and rarely culminates in cardiomyopathy.
Sources: Expert list
Hereditary Neuropathy - complex v0.166 ATAD3A Sangavi Sivagnanasundram changed review comment from: Is a syndromic neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, truncal hypotonia, spasticity, and peripheral neuropathy.

Neuropathy like phenotypes are only present in individuals with monoallelic variants in ATAD3A

PMID: 27640307
5 affected individuals from 5 unrelated families with the recurrent heterozygous de novo mutation (p.Arg528Trp) with all individuals presenting with symptoms of peripheral neuropathy.

Fly functional study conducted that showed a dramatic reduction in survival in the presence of the mutant protein suggesting it is highly toxic.
The loss of function phenotype assiociated with bor was assessed by performing transmission electron microscopy (TEM) on the first larvae prior to their death and identified a dramatic decrease in mitochondrial content indicating a similarity in phenotype for both LoF and GoF.Therefore the mode of pathogenicity is suggestive of dominant negative.

AR inheritance is due to loss of function mutations in ATAD3A and is typically infantile onset.; to: Is a syndromic neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, truncal hypotonia, spasticity, and peripheral neuropathy.

Neuropathy like phenotypes are only present in individuals with monoallelic variants in ATAD3A

PMID: 27640307
5 affected individuals from 5 unrelated families with the recurrent heterozygous de novo mutation (p.Arg528Trp) with all individuals presenting with symptoms of peripheral neuropathy.

Fly functional study conducted that showed a dramatic reduction in survival in the presence of the mutant protein suggesting it is highly toxic. The loss of function phenotype assiociated with bor was assessed by performing transmission electron microscopy (TEM) on the first larvae prior to their death and identified a dramatic decrease in mitochondrial content indicating a similarity in phenotype for both LoF and GoF.Therefore the mode of pathogenicity is suggestive of dominant negative.

AR inheritance is due to loss of function mutations in ATAD3A and is typically infantile onset.
Hereditary Neuropathy - complex v0.166 ATAD3A Sangavi Sivagnanasundram changed review comment from: Is a syndromic neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, truncal hypotonia, spasticity, and peripheral neuropathy.

Neuropathy like phenotypes are only present in individuals with monoallelic variants in ATAD3A

PMID: 27640307
5 affected individuals from 5 unrelated families with the recurrent heterozygous de novo mutation (p.Arg528Trp) with all individuals presenting with symptoms of peripheral neuropathy.

Fly functional study conducted that showed a dramatic reduction in survival in the presence of the mutant protein suggesting it is highly toxic.
The loss of function phenotype assiociated with bor was assessed by performing transmission electron microscopy (TEM) on the first larvae prior to their death and identified a dramatic decrease in mitochondrial content indicating a similarity in phenotype for bothe LoF and GoF.
Therefore the mode of pathogenicity is suggestive of dominant negative.

AR inheritance is due to loss of function mutations in ATAD3A and is typically infantile onset.; to: Is a syndromic neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, truncal hypotonia, spasticity, and peripheral neuropathy.

Neuropathy like phenotypes are only present in individuals with monoallelic variants in ATAD3A

PMID: 27640307
5 affected individuals from 5 unrelated families with the recurrent heterozygous de novo mutation (p.Arg528Trp) with all individuals presenting with symptoms of peripheral neuropathy.

Fly functional study conducted that showed a dramatic reduction in survival in the presence of the mutant protein suggesting it is highly toxic.
The loss of function phenotype assiociated with bor was assessed by performing transmission electron microscopy (TEM) on the first larvae prior to their death and identified a dramatic decrease in mitochondrial content indicating a similarity in phenotype for both LoF and GoF.Therefore the mode of pathogenicity is suggestive of dominant negative.

AR inheritance is due to loss of function mutations in ATAD3A and is typically infantile onset.
Hereditary Neuropathy - complex v0.166 ATAD3A Sangavi Sivagnanasundram reviewed gene: ATAD3A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 27640307; Phenotypes: Harel-Yoon Syndrome (MIM#6173183); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.174 MYL1 Sangavi Sivagnanasundram edited their review of gene: MYL1: Changed publications: 30215711
Incidentalome v0.232 POT1 Zornitza Stark Marked gene: POT1 as ready
Incidentalome v0.232 POT1 Zornitza Stark Gene: pot1 has been classified as Green List (High Evidence).
Incidentalome v0.232 POT1 Zornitza Stark Phenotypes for gene: POT1 were changed from Tumour predisposition with variety of solid and haematological malignancies reported. to Hereditary neoplastic syndrome, MONDO:0015356, POT1-related
Incidentalome v0.231 POT1 Zornitza Stark Classified gene: POT1 as Green List (high evidence)
Incidentalome v0.231 POT1 Zornitza Stark Gene: pot1 has been classified as Green List (High Evidence).
Incidentalome v0.230 POT1 Zornitza Stark Tag cancer tag was added to gene: POT1.
Incidentalome v0.230 POT1 Zornitza Stark reviewed gene: POT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hereditary neoplastic syndrome, MONDO:0015356, POT1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.230 POT1 Edward Chew gene: POT1 was added
gene: POT1 was added to Incidentalome. Sources: Expert list
Mode of inheritance for gene: POT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POT1 were set to (PMID:27528712; PMID: 29693246; PMID: 34769003; PMID: 36467798; PMID: 33216348; PMID: 24686849; PMID:24686846; PMID: 26403419; PMID: 32492864)
Phenotypes for gene: POT1 were set to Tumour predisposition with variety of solid and haematological malignancies reported.
Penetrance for gene: POT1 were set to Incomplete
Review for gene: POT1 was set to GREEN
Added comment: CLL (PMID: 27528712, published 2016) identified 4 families with POT1 variants and CLL.
Aberrant splicing of intron 13 (chromosome 7 g.124481233C.T/c.1164-1G.A) confirmed by RT-PCR. Missense p.Tyr36Cys and p.Gln376Arg predicted to be pathogenic by in silico methods. p.Gln358SerfsTer13 predicted to cause premature truncation.

Hodgkin Lymphoma (PMID: 29693246, published 2018) identified 2 families with POT1 variants and Hodgkin lymphoma.
p.Asp224Asn in 4 carriers with Hodgkin lymphoma. Variant validated functionally.
p.Tryp26His in 2 carriers with Hodgkin lymphoma. Some functional validation performed.

AML (PMID: 34769003, published 2021) identified p.Q199* in a 8yo with AML and monosomy 7. Unaffected father, de novo status of variant not confirmed. Some functional validation (but conflicting).

Multiple myeloma (PMID: 36467798, published 2022) looked at inherited predisposition for multiple myeloma. Identified 4 families with POT1 variants who have myeloma, thyroid cancer, and AML. Functional validation not performed.

Multiple haematological malignancies, cutaneous melanoma and solid cancers in a family from Queensland (PMID: 33216348, published 2020). The variant p.D224N has been reported and functionally validated by other authors.

Cutaneous melanoma (PMID: 24686849; PMID:24686846, published in same issue of journal in 2014) identified families with strong family history of melanoma. PMID: 24686849 identified 4 families with 4 different POT1 variants. PMID 24686846 identified 5 families with same founder p.Ser270Asn variant. Functional validation of pathogenicity performed in the 2 papers.

Li-Fraumeni Like syndrome (PMID: 26403419 published 2015) identified 3 families with p.R117C variant and strong family history of Li-Fraumeni Like syndrome. Variant functionally validated.

Medullary thyroid cancer (PMID: 32492864 published 2020) identified 1 family with p.V29L. The variant segregates with papillary thyroid cancer. Some functional validation performed.
Sources: Expert list
Muscular dystrophy and myopathy_Paediatric v0.174 TRIP4 Bryony Thompson Marked gene: TRIP4 as ready
Muscular dystrophy and myopathy_Paediatric v0.174 TRIP4 Bryony Thompson Gene: trip4 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.174 TRIP4 Bryony Thompson Classified gene: TRIP4 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.174 TRIP4 Bryony Thompson Gene: trip4 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.173 TPM3 Bryony Thompson Marked gene: TPM3 as ready
Muscular dystrophy and myopathy_Paediatric v0.173 TPM3 Bryony Thompson Gene: tpm3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.173 TPM3 Bryony Thompson Classified gene: TPM3 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.173 TPM3 Bryony Thompson Gene: tpm3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.172 TPM2 Bryony Thompson Marked gene: TPM2 as ready
Muscular dystrophy and myopathy_Paediatric v0.172 TPM2 Bryony Thompson Gene: tpm2 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.172 TPM2 Bryony Thompson Classified gene: TPM2 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.172 TPM2 Bryony Thompson Gene: tpm2 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.171 TNNC2 Bryony Thompson Marked gene: TNNC2 as ready
Muscular dystrophy and myopathy_Paediatric v0.171 TNNC2 Bryony Thompson Gene: tnnc2 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.171 TNNC2 Bryony Thompson Classified gene: TNNC2 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v0.171 TNNC2 Bryony Thompson Gene: tnnc2 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.170 STAC3 Bryony Thompson Marked gene: STAC3 as ready
Muscular dystrophy and myopathy_Paediatric v0.170 STAC3 Bryony Thompson Gene: stac3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.170 STAC3 Bryony Thompson Classified gene: STAC3 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.170 STAC3 Bryony Thompson Gene: stac3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.169 SPEG Bryony Thompson Marked gene: SPEG as ready
Muscular dystrophy and myopathy_Paediatric v0.169 SPEG Bryony Thompson Gene: speg has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.169 SPEG Bryony Thompson Classified gene: SPEG as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.169 SPEG Bryony Thompson Gene: speg has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.168 PAX7 Bryony Thompson Marked gene: PAX7 as ready
Muscular dystrophy and myopathy_Paediatric v0.168 PAX7 Bryony Thompson Gene: pax7 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.168 PAX7 Bryony Thompson Classified gene: PAX7 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.168 PAX7 Bryony Thompson Gene: pax7 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.167 NEB Bryony Thompson Marked gene: NEB as ready
Muscular dystrophy and myopathy_Paediatric v0.167 NEB Bryony Thompson Gene: neb has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.167 NEB Bryony Thompson Classified gene: NEB as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.167 NEB Bryony Thompson Gene: neb has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.166 MYPN Bryony Thompson Marked gene: MYPN as ready
Muscular dystrophy and myopathy_Paediatric v0.166 MYPN Bryony Thompson Gene: mypn has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.166 MYPN Bryony Thompson Classified gene: MYPN as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.166 MYPN Bryony Thompson Gene: mypn has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.165 MYOD1 Bryony Thompson Marked gene: MYOD1 as ready
Muscular dystrophy and myopathy_Paediatric v0.165 MYOD1 Bryony Thompson Gene: myod1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.165 MYOD1 Bryony Thompson Classified gene: MYOD1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.165 MYOD1 Bryony Thompson Gene: myod1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.164 MYL1 Bryony Thompson Marked gene: MYL1 as ready
Muscular dystrophy and myopathy_Paediatric v0.164 MYL1 Bryony Thompson Gene: myl1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.164 MYL1 Bryony Thompson Classified gene: MYL1 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v0.164 MYL1 Bryony Thompson Gene: myl1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.163 MYL1 Bryony Thompson Publications for gene: MYL1 were set to 30275711
Muscular dystrophy and myopathy_Paediatric v0.162 MYBPC1 Bryony Thompson Marked gene: MYBPC1 as ready
Muscular dystrophy and myopathy_Paediatric v0.162 MYBPC1 Bryony Thompson Gene: mybpc1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.162 MYBPC1 Bryony Thompson Classified gene: MYBPC1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.162 MYBPC1 Bryony Thompson Gene: mybpc1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.161 MTMR14 Bryony Thompson Marked gene: MTMR14 as ready
Muscular dystrophy and myopathy_Paediatric v0.161 MTMR14 Bryony Thompson Gene: mtmr14 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.161 MTMR14 Bryony Thompson Classified gene: MTMR14 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v0.161 MTMR14 Bryony Thompson Gene: mtmr14 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.928 NFATC1 Zornitza Stark Marked gene: NFATC1 as ready
Mendeliome v1.928 NFATC1 Zornitza Stark Gene: nfatc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.928 NFATC1 Zornitza Stark Classified gene: NFATC1 as Amber List (moderate evidence)
Mendeliome v1.928 NFATC1 Zornitza Stark Gene: nfatc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.927 NFATC1 Zornitza Stark gene: NFATC1 was added
gene: NFATC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NFATC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFATC1 were set to 37249233
Phenotypes for gene: NFATC1 were set to Inborn error of immunity, MONDO:0003778, NFATC1-related; Combined Immune deficiency
Review for gene: NFATC1 was set to AMBER
Added comment: 3 individuals from a multigenerational consanguineous pedigree with early-onset sinopulmonary infections and bronchiectasis, recurrent viral (warts) and bacterial (folliculitis and abscesses) skin infections, hypogammaglobulinemia, lower CD4+/CD8+ T-cell ratio and lower recent thymic emigrants compared with the age-matched controls. Lymphocyte proliferation responses to PHA and CD3/CD28 stimulations were defective.

Single pedigree with supportive functional studies.
Sources: Literature
Combined Immunodeficiency v1.39 NFATC1 Zornitza Stark Marked gene: NFATC1 as ready
Combined Immunodeficiency v1.39 NFATC1 Zornitza Stark Gene: nfatc1 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.39 NFATC1 Zornitza Stark Phenotypes for gene: NFATC1 were changed from Combined Immune deficiency to Inborn error of immunity, MONDO:0003778, NFATC1-related; Combined Immune deficiency
Combined Immunodeficiency v1.38 NFATC1 Zornitza Stark Classified gene: NFATC1 as Amber List (moderate evidence)
Combined Immunodeficiency v1.38 NFATC1 Zornitza Stark Gene: nfatc1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.160 MAP3K20 Bryony Thompson Marked gene: MAP3K20 as ready
Muscular dystrophy and myopathy_Paediatric v0.160 MAP3K20 Bryony Thompson Gene: map3k20 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.160 MAP3K20 Bryony Thompson Classified gene: MAP3K20 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.160 MAP3K20 Bryony Thompson Gene: map3k20 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.159 LMOD3 Bryony Thompson Marked gene: LMOD3 as ready
Muscular dystrophy and myopathy_Paediatric v0.159 LMOD3 Bryony Thompson Gene: lmod3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.159 LMOD3 Bryony Thompson Classified gene: LMOD3 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.159 LMOD3 Bryony Thompson Gene: lmod3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.158 KLHL41 Bryony Thompson Marked gene: KLHL41 as ready
Muscular dystrophy and myopathy_Paediatric v0.158 KLHL41 Bryony Thompson Gene: klhl41 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.158 KLHL41 Bryony Thompson Classified gene: KLHL41 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.158 KLHL41 Bryony Thompson Gene: klhl41 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.157 KLHL40 Bryony Thompson Marked gene: KLHL40 as ready
Muscular dystrophy and myopathy_Paediatric v0.157 KLHL40 Bryony Thompson Gene: klhl40 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.157 KLHL40 Bryony Thompson Classified gene: KLHL40 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.157 KLHL40 Bryony Thompson Gene: klhl40 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.156 KBTBD13 Bryony Thompson Marked gene: KBTBD13 as ready
Muscular dystrophy and myopathy_Paediatric v0.156 KBTBD13 Bryony Thompson Gene: kbtbd13 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.156 KBTBD13 Bryony Thompson Classified gene: KBTBD13 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.156 KBTBD13 Bryony Thompson Gene: kbtbd13 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.155 HRAS Bryony Thompson Marked gene: HRAS as ready
Muscular dystrophy and myopathy_Paediatric v0.155 HRAS Bryony Thompson Gene: hras has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.155 HRAS Bryony Thompson Classified gene: HRAS as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v0.155 HRAS Bryony Thompson Gene: hras has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.154 EPG5 Sangavi Sivagnanasundram edited their review of gene: EPG5: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.154 HACD1 Bryony Thompson Marked gene: HACD1 as ready
Muscular dystrophy and myopathy_Paediatric v0.154 HACD1 Bryony Thompson Gene: hacd1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.154 HACD1 Bryony Thompson Classified gene: HACD1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.154 HACD1 Bryony Thompson Gene: hacd1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.153 FXR1 Bryony Thompson Marked gene: FXR1 as ready
Muscular dystrophy and myopathy_Paediatric v0.153 FXR1 Bryony Thompson Gene: fxr1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.153 FXR1 Bryony Thompson Classified gene: FXR1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.153 FXR1 Bryony Thompson Gene: fxr1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.152 EPG5 Bryony Thompson Marked gene: EPG5 as ready
Muscular dystrophy and myopathy_Paediatric v0.152 EPG5 Bryony Thompson Gene: epg5 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.152 EPG5 Bryony Thompson Classified gene: EPG5 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.152 EPG5 Bryony Thompson Gene: epg5 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.151 EPG5 Bryony Thompson Mode of inheritance for gene: EPG5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.150 DYNC1H1 Bryony Thompson Marked gene: DYNC1H1 as ready
Muscular dystrophy and myopathy_Paediatric v0.150 DYNC1H1 Bryony Thompson Gene: dync1h1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.150 DYNC1H1 Bryony Thompson Classified gene: DYNC1H1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.150 DYNC1H1 Bryony Thompson Gene: dync1h1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.149 DNM2 Bryony Thompson Marked gene: DNM2 as ready
Muscular dystrophy and myopathy_Paediatric v0.149 DNM2 Bryony Thompson Gene: dnm2 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.149 DNM2 Bryony Thompson Classified gene: DNM2 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.149 DNM2 Bryony Thompson Gene: dnm2 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.148 DHX16 Bryony Thompson Marked gene: DHX16 as ready
Muscular dystrophy and myopathy_Paediatric v0.148 DHX16 Bryony Thompson Gene: dhx16 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.148 DHX16 Bryony Thompson Classified gene: DHX16 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v0.148 DHX16 Bryony Thompson Gene: dhx16 has been classified as Red List (Low Evidence).
Mendeliome v1.926 CNTN1 Bryony Thompson Phenotypes for gene: CNTN1 were changed from Myopathy, congenital, Compton-North 612540 to Compton-North congenital myopathy MONDO:0012929; fetal akinesia deformation sequence MONDO:0008824
Muscular dystrophy and myopathy_Paediatric v0.147 CNTN1 Bryony Thompson Marked gene: CNTN1 as ready
Muscular dystrophy and myopathy_Paediatric v0.147 CNTN1 Bryony Thompson Gene: cntn1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.147 CNTN1 Bryony Thompson Classified gene: CNTN1 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v0.147 CNTN1 Bryony Thompson Gene: cntn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.925 CNTN1 Bryony Thompson Publications for gene: CNTN1 were set to 19026398
Mendeliome v1.924 CNTN1 Bryony Thompson Classified gene: CNTN1 as Green List (high evidence)
Mendeliome v1.924 CNTN1 Bryony Thompson Gene: cntn1 has been classified as Green List (High Evidence).
Mendeliome v1.923 CNTN1 Bryony Thompson reviewed gene: CNTN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19026398, 10595523, 22242131, 32779773; Phenotypes: Compton-North congenital myopathy MONDO:0012929, fetal akinesia deformation sequence MONDO:0008824; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.2175 PDP1 Zornitza Stark Marked gene: PDP1 as ready
Genomic newborn screening: BabyScreen+ v0.2175 PDP1 Zornitza Stark Gene: pdp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2175 PDP1 Zornitza Stark Phenotypes for gene: PDP1 were changed from Pyruvate dehydrogenase phosphatase deficiency to Pyruvate dehydrogenase phosphatase deficiency, MIM# 608782
Genomic newborn screening: BabyScreen+ v0.2174 PDP1 Zornitza Stark Classified gene: PDP1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2174 PDP1 Zornitza Stark Gene: pdp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2174 PDP1 Zornitza Stark Classified gene: PDP1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2174 PDP1 Zornitza Stark Gene: pdp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2173 PDP1 Zornitza Stark reviewed gene: PDP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pyruvate dehydrogenase phosphatase deficiency, MIM# 608782; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.2173 DLAT Zornitza Stark Marked gene: DLAT as ready
Genomic newborn screening: BabyScreen+ v0.2173 DLAT Zornitza Stark Gene: dlat has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2173 DLAT Zornitza Stark Classified gene: DLAT as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2173 DLAT Zornitza Stark Gene: dlat has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2172 DLAT Zornitza Stark gene: DLAT was added
gene: DLAT was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: DLAT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DLAT were set to Pyruvate dehydrogenase E2 deficiency, MIM# 245348
Review for gene: DLAT was set to GREEN
Added comment: Well established gene-disease association.

Clinical presentation is in infancy.

Treatment: ketogenic diet has a significant impact on outcome; some cases responsive to thiamine

Non-genetic confirmatory testing: enzymology

Included for consistency with PDHA1/PDHX
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.2171 PDHB Zornitza Stark Marked gene: PDHB as ready
Genomic newborn screening: BabyScreen+ v0.2171 PDHB Zornitza Stark Gene: pdhb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2171 PDHB Zornitza Stark Classified gene: PDHB as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2171 PDHB Zornitza Stark Gene: pdhb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2170 PDHB Zornitza Stark gene: PDHB was added
gene: PDHB was added to Baby Screen+ newborn screening. Sources: Expert Review
treatable, metabolic tags were added to gene: PDHB.
Mode of inheritance for gene: PDHB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PDHB were set to Pyruvate dehydrogenase E1-beta deficiency, MIM# 614111
Review for gene: PDHB was set to GREEN
Added comment: Well established gene-disease association.

Clinical presentation is in infancy.

Treatment: ketogenic diet has a significant impact on outcome; some cases responsive to thiamine

Non-genetic confirmatory testing: enzymology

Included for consistency with PDHA1/PDHX
Sources: Expert Review
Mendeliome v1.923 TNNT1 Zornitza Stark Phenotypes for gene: TNNT1 were changed from Nemaline myopathy 5, Amish type, MIM# 605355; nemaline myopathy MONDO:0018958 to Nemaline myopathy 5, Amish type, MIM# 605355; Nemaline myopathy-5B with rigid spine and respiratory insufficiency (NEM5B), MIM#620386; nemaline myopathy-5C (NEM5C), autosomal dominant, MIMD620389
Mendeliome v1.922 TNNT1 Zornitza Stark edited their review of gene: TNNT1: Changed phenotypes: Nemaline myopathy 5, Amish type, MIM# 605355, Nemaline myopathy-5B with rigid spine and respiratory insufficiency (NEM5B), MIM#620386, nemaline myopathy-5C (NEM5C), autosomal dominant, MIMD620389
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.130 CHRM5 Zornitza Stark Marked gene: CHRM5 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.130 CHRM5 Zornitza Stark Gene: chrm5 has been classified as Red List (Low Evidence).
Mendeliome v1.922 CHRM5 Zornitza Stark Marked gene: CHRM5 as ready
Mendeliome v1.922 CHRM5 Zornitza Stark Gene: chrm5 has been classified as Red List (Low Evidence).
Severe early-onset obesity v1.9 ACBD6 Zornitza Stark Marked gene: ACBD6 as ready
Severe early-onset obesity v1.9 ACBD6 Zornitza Stark Gene: acbd6 has been classified as Amber List (Moderate Evidence).
Severe early-onset obesity v1.9 ACBD6 Zornitza Stark Classified gene: ACBD6 as Amber List (moderate evidence)
Severe early-onset obesity v1.9 ACBD6 Zornitza Stark Gene: acbd6 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.311 MRPL50 Zornitza Stark Marked gene: MRPL50 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.311 MRPL50 Zornitza Stark Gene: mrpl50 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.311 MRPL50 Zornitza Stark Classified gene: MRPL50 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.311 MRPL50 Zornitza Stark Gene: mrpl50 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.875 MRPL50 Zornitza Stark Marked gene: MRPL50 as ready
Mitochondrial disease v0.875 MRPL50 Zornitza Stark Gene: mrpl50 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.875 MRPL50 Zornitza Stark Classified gene: MRPL50 as Amber List (moderate evidence)
Mitochondrial disease v0.875 MRPL50 Zornitza Stark Gene: mrpl50 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.922 MRPL50 Zornitza Stark Marked gene: MRPL50 as ready
Mendeliome v1.922 MRPL50 Zornitza Stark Gene: mrpl50 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.922 MRPL50 Zornitza Stark Classified gene: MRPL50 as Amber List (moderate evidence)
Mendeliome v1.922 MRPL50 Zornitza Stark Gene: mrpl50 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.921 MRPL50 Zornitza Stark reviewed gene: MRPL50: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial disease, MONDO: 004470, MRPL50-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.113 KIF26A Zornitza Stark Marked gene: KIF26A as ready
Fetal anomalies v1.113 KIF26A Zornitza Stark Gene: kif26a has been classified as Green List (High Evidence).
Fetal anomalies v1.113 KIF26A Zornitza Stark Classified gene: KIF26A as Green List (high evidence)
Fetal anomalies v1.113 KIF26A Zornitza Stark Gene: kif26a has been classified as Green List (High Evidence).
Fetal anomalies v1.112 KIF26A Zornitza Stark gene: KIF26A was added
gene: KIF26A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KIF26A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF26A were set to 36564622
Phenotypes for gene: KIF26A were set to Cortical dysplasia, complex, with other brain malformations 11, MIM# 620156
Review for gene: KIF26A was set to GREEN
Added comment: Five individuals from two families each with a different homozygous truncating variant in KIF26A segregating with profound ENS dysfunction that manifested clinically like Hirschsprung’s disease despite normal ganglionosis. Moreover, they all have neurological involvement with brain malformations ranging from ventriculomegaly to severe congenital hydrocephalus in two siblings who died early in life. Clinically, they displayed developmental delay and, in the longest surviving individual, spastic paraplegia.

Brain abnormalities may be detectable antenatally.
Sources: Literature
Hirschsprung disease v0.25 KIF26A Zornitza Stark Marked gene: KIF26A as ready
Hirschsprung disease v0.25 KIF26A Zornitza Stark Gene: kif26a has been classified as Green List (High Evidence).
Hirschsprung disease v0.25 KIF26A Zornitza Stark Classified gene: KIF26A as Green List (high evidence)
Hirschsprung disease v0.25 KIF26A Zornitza Stark Gene: kif26a has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.120 KIF26A Zornitza Stark Marked gene: KIF26A as ready
Hydrocephalus_Ventriculomegaly v0.120 KIF26A Zornitza Stark Gene: kif26a has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.120 KIF26A Zornitza Stark Classified gene: KIF26A as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v0.120 KIF26A Zornitza Stark Gene: kif26a has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.107 TAPT1 Zornitza Stark Publications for gene: TAPT1 were set to 26365339
Mendeliome v1.921 MOS Zornitza Stark Marked gene: MOS as ready
Mendeliome v1.921 MOS Zornitza Stark Gene: mos has been classified as Green List (High Evidence).
Mendeliome v1.921 MOS Zornitza Stark Phenotypes for gene: MOS were changed from Early embryonic arrest and fragmentation; infertility to Infertility disorder, MONDO:0005047, MOS-related; Early embryonic arrest and fragmentation
Combined Immunodeficiency v1.37 NFATC1 Peter McNaughton gene: NFATC1 was added
gene: NFATC1 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: NFATC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFATC1 were set to PMID: 37249233
Phenotypes for gene: NFATC1 were set to Combined Immune deficiency
Review for gene: NFATC1 was set to AMBER
Added comment: 3 patients from a multigenerational consanguineous pedigree with early-onset sinopulmonary infections and bronchiectasis, recurrent viral (warts) and bacterial (folliculitis and abscesses) skin infections, hypogammaglobulinemia, lower CD4+/CD8+ T-cell ratio and lower recent thymic emigrants compared with the age-matched controls. Lymphocyte proliferation responses to PHA and CD3/CD28 stimulations were defective.
Single pedigree but supportive functional studies - ?green.
Sources: Literature
Mendeliome v1.920 MOS Zornitza Stark Classified gene: MOS as Green List (high evidence)
Mendeliome v1.920 MOS Zornitza Stark Gene: mos has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.146 HMGCR Zornitza Stark Marked gene: HMGCR as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.146 HMGCR Zornitza Stark Gene: hmgcr has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.146 HMGCR Zornitza Stark Classified gene: HMGCR as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.146 HMGCR Zornitza Stark Gene: hmgcr has been classified as Green List (High Evidence).
Mendeliome v1.919 HMGCR Zornitza Stark Phenotypes for gene: HMGCR were changed from [Low density lipoprotein cholesterol level QTL 3] to autosomal recessive limb-girdle muscular dystrophy (MONDO: 0015152), HMGCR-related
Mendeliome v1.918 HMGCR Zornitza Stark Publications for gene: HMGCR were set to 18354102; 29480216
Mendeliome v1.917 HMGCR Zornitza Stark Mode of inheritance for gene: HMGCR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.916 HMGCR Zornitza Stark Classified gene: HMGCR as Green List (high evidence)
Mendeliome v1.916 HMGCR Zornitza Stark Gene: hmgcr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5244 MCM6 Zornitza Stark Marked gene: MCM6 as ready
Intellectual disability syndromic and non-syndromic v0.5244 MCM6 Zornitza Stark Gene: mcm6 has been classified as Green List (High Evidence).
Mendeliome v1.915 MOS Melanie Marty gene: MOS was added
gene: MOS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MOS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOS were set to PMID: 34779126; PMID: 34997960; PMID: 36403623; PMID: 35670744
Phenotypes for gene: MOS were set to Early embryonic arrest and fragmentation; infertility
Review for gene: MOS was set to GREEN
Added comment: PMID: 34779126: 3 x females with infertility with biallelic MOS variants identified. Using oocyte-specific Erk1/2 knockout mice, they verified that MOS-ERK signal pathway inactivation in oocytes caused early embryonic arrest and fragmentation.

PMID: 34997960: 2 x females with biallelic MOS variants. Functional studies showed a reduction of protein for two of these variants (missense and frameshift). Functional studies also showed these variants reduced the ability of MOS to phosphorylate its downstream target, extracellular signal-regulated kinase 1/2.

PMID: 35670744 1 x additional family (twins) with infertility and abnormal oocyte morphology with large first polar body. Functional studies showed the MOS variants could not activate MEK1/2 and ERK1/2 in oocytes and HEK293 cells. In addition, functional studies also showed when compared with wild-type MOS, the MOS variants decreased the MOS protein level and attenuated the binding capacity with MEK1.

PMID: 36403623 1 x female with primary infertility, patient’s oocytes had a large polar body and poor embryonic development, hom missense variant in MOS identified.
Sources: Literature
Osteogenesis Imperfecta and Osteoporosis v0.106 TAPT1 Paul De Fazio reviewed gene: TAPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36697720, 36652330; Phenotypes: Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897); Mode of inheritance: None; Current diagnostic: yes
Genetic Epilepsy v0.1862 ANK2 Elena Savva Phenotypes for gene: ANK2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, ANK2-related to Complex neurodevelopmental disorder, MONDO:0100038, ANK2-related
Genetic Epilepsy v0.1861 ANK2 Elena Savva Phenotypes for gene: ANK2 were changed from Complex neurodevelopmental disorder, MONDO:0100038, ANK2-related to Complex neurodevelopmental disorder, MONDO:0100038, ANK2-related
Genetic Epilepsy v0.1860 ANK2 Elena Savva Phenotypes for gene: ANK2 were changed from Epilepsy, MONDO:0005027, Complex neurodevelopmental disorder, MONDO:0100038 to Complex neurodevelopmental disorder, MONDO:0100038, ANK2-related
Genetic Epilepsy v0.1859 ANK2 Elena Savva Marked gene: ANK2 as ready
Genetic Epilepsy v0.1859 ANK2 Elena Savva Gene: ank2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1859 ANK2 Elena Savva Classified gene: ANK2 as Green List (high evidence)
Genetic Epilepsy v0.1859 ANK2 Elena Savva Gene: ank2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1858 ANK2 Elena Savva Classified gene: ANK2 as Green List (high evidence)
Genetic Epilepsy v0.1858 ANK2 Elena Savva Gene: ank2 has been classified as Green List (High Evidence).
Cataract v0.355 TAPT1 Ain Roesley Marked gene: TAPT1 as ready
Cataract v0.355 TAPT1 Ain Roesley Gene: tapt1 has been classified as Red List (Low Evidence).
Cataract v0.355 TAPT1 Ain Roesley Classified gene: TAPT1 as Red List (low evidence)
Cataract v0.355 TAPT1 Ain Roesley Gene: tapt1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5244 UNC79 Zornitza Stark Phenotypes for gene: UNC79 were changed from Neurodevelopmental disorder (MONDO:0700092), UNC79-related to Neurodevelopmental disorder (MONDO:0700092), UNC79-related
Intellectual disability syndromic and non-syndromic v0.5243 UNC79 Elena Savva Phenotypes for gene: UNC79 were changed from Neurodevelopmental disorder (MONDO:0700092), UNC79-related to Neurodevelopmental disorder (MONDO:0700092), UNC79-related
Intellectual disability syndromic and non-syndromic v0.5243 UNC79 Zornitza Stark Phenotypes for gene: UNC79 were changed from Neurodevelopmental disorder (MONDO:0700092), UNC70-related to Neurodevelopmental disorder (MONDO:0700092), UNC79-related
Genetic Epilepsy v0.1857 UNC79 Zornitza Stark Phenotypes for gene: UNC79 were changed from Neurodevelopmental disorder (MONDO:0700092), UNC70-related to Neurodevelopmental disorder (MONDO:0700092), UNC79-related
Mendeliome v1.915 TAPT1 Elena Savva Publications for gene: TAPT1 were set to 26365339
Skeletal dysplasia v0.233 TAPT1 Elena Savva Publications for gene: TAPT1 were set to 26365339
Mendeliome v1.914 UNC79 Zornitza Stark Phenotypes for gene: UNC79 were changed from Neurodevelopmental disorder (MONDO:0700092), UNC70-related to Neurodevelopmental disorder (MONDO:0700092), UNC79-related
Cataract v0.354 TAPT1 Paul De Fazio gene: TAPT1 was added
gene: TAPT1 was added to Cataract. Sources: Literature
Mode of inheritance for gene: TAPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAPT1 were set to 36697720; 36652330
Phenotypes for gene: TAPT1 were set to Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897)
Review for gene: TAPT1 was set to RED
gene: TAPT1 was marked as current diagnostic
Added comment: PMID: 36697720 - reports a patient with a biallelic frameshift variant in an infant with bilateral cateract, dysmorphic features, poor weight gain, and clinical symptoms reminiscent of osteogenesis imperfecta. A zebrafish knockout model showed aberrant lens development but no visible skeletal involvement.
Sources: Literature
Mendeliome v1.913 NSUN6 Elena Savva Classified gene: NSUN6 as Amber List (moderate evidence)
Mendeliome v1.913 NSUN6 Elena Savva Gene: nsun6 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.912 NSUN6 Elena Savva Classified gene: NSUN6 as Amber List (moderate evidence)
Mendeliome v1.912 NSUN6 Elena Savva Gene: nsun6 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.911 NSUN6 Elena Savva Marked gene: NSUN6 as ready
Mendeliome v1.911 NSUN6 Elena Savva Gene: nsun6 has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.5242 NSUN6 Elena Savva Classified gene: NSUN6 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5242 NSUN6 Elena Savva Gene: nsun6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5241 NSUN6 Elena Savva Marked gene: NSUN6 as ready
Intellectual disability syndromic and non-syndromic v0.5241 NSUN6 Elena Savva Gene: nsun6 has been removed from the panel.
Mendeliome v1.911 TAPT1 Paul De Fazio reviewed gene: TAPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36697720, 36652330; Phenotypes: Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v0.1856 UNC79 Elena Savva Phenotypes for gene: UNC79 were changed from Neurodevelopmental disorder (MONDO:0700092), UNC70-related to Neurodevelopmental disorder (MONDO:0700092), UNC70-related
Skeletal dysplasia v0.232 TAPT1 Paul De Fazio reviewed gene: TAPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36697720, 36652330; Phenotypes: Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v0.1856 UNC79 Elena Savva Phenotypes for gene: UNC79 were changed from Neurodevelopmental disorder (MONDO:0700092), UNC70-related to Neurodevelopmental disorder (MONDO:0700092), UNC70-related
Mendeliome v1.911 PRSS8 Elena Savva Classified gene: PRSS8 as Amber List (moderate evidence)
Mendeliome v1.911 PRSS8 Elena Savva Gene: prss8 has been classified as Amber List (Moderate Evidence).
Ichthyosis v1.4 PRSS8 Elena Savva Classified gene: PRSS8 as Amber List (moderate evidence)
Ichthyosis v1.4 PRSS8 Elena Savva Gene: prss8 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.910 PRSS8 Elena Savva Marked gene: PRSS8 as ready
Mendeliome v1.910 PRSS8 Elena Savva Gene: prss8 has been removed from the panel.
Genetic Epilepsy v0.1856 UNC79 Elena Savva Phenotypes for gene: UNC79 were changed from Neurodevelopmental disorder (MONDO:0700092), UNC70-related to Neurodevelopmental disorder (MONDO:0700092), UNC70-related
Ichthyosis v1.3 PRSS8 Elena Savva Marked gene: PRSS8 as ready
Ichthyosis v1.3 PRSS8 Elena Savva Gene: prss8 has been removed from the panel.
Regression v0.527 RNH1 Ain Roesley Publications for gene: RNH1 were set to PMID: 36935417; 37191094
Genetic Epilepsy v0.1855 UNC79 Elena Savva Classified gene: UNC79 as Green List (high evidence)
Genetic Epilepsy v0.1855 UNC79 Elena Savva Gene: unc79 has been classified as Green List (High Evidence).
Mendeliome v1.910 RNH1 Ain Roesley Phenotypes for gene: RNH1 were changed from Neurodevelopmental disorder, MONDO:0700092, RNH1-related to Neurodevelopmental disorder, MONDO:0700092, RNH1-related; encephalopathy, acute, infection-induced (MONDO:0000166), RNH1-related
Regression v0.527 RNH1 Ain Roesley Phenotypes for gene: RNH1 were changed from Neurodevelopmental disorder, MONDO:0700092, RNH1-related; encephalopathy, acute, infection-induced (MONDO:0000166), RNH1-related to Neurodevelopmental disorder, MONDO:0700092, RNH1-related; encephalopathy, acute, infection-induced (MONDO:0000166), RNH1-related
Intellectual disability syndromic and non-syndromic v0.5241 UNC79 Elena Savva Classified gene: UNC79 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5241 UNC79 Elena Savva Gene: unc79 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1855 UNC79 Elena Savva Phenotypes for gene: UNC79 were changed from Complex neurodevelopmental disorder - MONDO:0100038 to Neurodevelopmental disorder (MONDO:0700092), UNC70-related
Mendeliome v1.909 RNH1 Ain Roesley Publications for gene: RNH1 were set to PMID: 36935417
Mendeliome v1.909 RNH1 Ain Roesley Classified gene: RNH1 as Green List (high evidence)
Mendeliome v1.909 RNH1 Ain Roesley Gene: rnh1 has been classified as Green List (High Evidence).
Mendeliome v1.908 PRSS8 Lucy Spencer gene: PRSS8 was added
gene: PRSS8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRSS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRSS8 were set to 36715754
Phenotypes for gene: PRSS8 were set to ichthyosis MONDO:0019269, PRSS8-related
Review for gene: PRSS8 was set to AMBER
Added comment: PMID: 36715754
1 family with 3 affected sons with congenital ichthyosis, consanguineous parents. All 3 affected members are homozygous for a canonical splice in PRSS8, quantitative RT-PCR showed a significant reduction in normal PRSS8 transcript.

A second family with 4 affected members (proband and 3 cousins) with ichthyosis (3 also had autism), also consanguineous. Only the proband was tested who is homozygous for a missense in PTSS8. However this patient also had a TAAR1 missense (no disease association, but the paper suggests this could be responsible for the autism phenotype- KO mice have abnormal learning behaviour).
Sources: Literature
Regression v0.526 RNH1 Ain Roesley Phenotypes for gene: RNH1 were changed from Neurodevelopmental disorder, MONDO:0700092, RNH1-related to Neurodevelopmental disorder, MONDO:0700092, RNH1-related; encephalopathy, acute, infection-induced (MONDO:0000166), RNH1-related
Intellectual disability syndromic and non-syndromic v0.5241 UNC79 Elena Savva Phenotypes for gene: UNC79 were changed from Neurodevelopmental disorder (MONDO:0700092), UNC70-related to Neurodevelopmental disorder (MONDO:0700092), UNC70-related
Genetic Epilepsy v0.1855 UNC79 Elena Savva Classified gene: UNC79 as Green List (high evidence)
Genetic Epilepsy v0.1855 UNC79 Elena Savva Gene: unc79 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5240 UNC79 Elena Savva Classified gene: UNC79 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5240 UNC79 Elena Savva Gene: unc79 has been classified as Green List (High Evidence).
Regression v0.526 RNH1 Ain Roesley Publications for gene: RNH1 were set to PMID: 36935417
Mendeliome v1.908 RNH1 Dean Phelan reviewed gene: RNH1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37191094; Phenotypes: encephalopathy, acute, infection-induced (MONDO:0000166), RNH1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5240 UNC79 Elena Savva Phenotypes for gene: UNC79 were changed from Complex neurodevelopmental disorder - MONDO:0100038 to Neurodevelopmental disorder (MONDO:0700092), UNC70-related
Genetic Epilepsy v0.1854 UNC79 Elena Savva Marked gene: UNC79 as ready
Genetic Epilepsy v0.1854 UNC79 Elena Savva Gene: unc79 has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.5239 UNC79 Elena Savva Marked gene: UNC79 as ready
Intellectual disability syndromic and non-syndromic v0.5239 UNC79 Elena Savva Gene: unc79 has been removed from the panel.
Mendeliome v1.908 UNC79 Elena Savva Marked gene: UNC79 as ready
Mendeliome v1.908 UNC79 Elena Savva Gene: unc79 has been classified as Green List (High Evidence).
Regression v0.526 RNH1 Ain Roesley Classified gene: RNH1 as Green List (high evidence)
Regression v0.526 RNH1 Ain Roesley Gene: rnh1 has been classified as Green List (High Evidence).
Mendeliome v1.908 UNC79 Elena Savva Phenotypes for gene: UNC79 were changed from Neurodevelopmental disorderMONDO:0700092 to Neurodevelopmental disorder (MONDO:0700092), UNC70-related
Ichthyosis v1.3 PRSS8 Lucy Spencer gene: PRSS8 was added
gene: PRSS8 was added to Ichthyosis. Sources: Literature
Mode of inheritance for gene: PRSS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRSS8 were set to 36715754
Phenotypes for gene: PRSS8 were set to ichthyosis MONDO:0019269, PRSS8-related
Review for gene: PRSS8 was set to AMBER
Added comment: PMID: 36715754
1 family with 3 affected sons with congenital ichthyosis, consanguineous parents. All 3 affected members are homozygous for a canonical splice in PRSS8, quantitative RT-PCR showed a significant reduction in normal PRSS8 transcript.

A second family with 4 affected members (proband and 3 cousins) with ichthyosis (3 also had autism), also consanguineous. Only the proband was tested who is homozygous for a missense in PTSS8. However this patient also had a TAAR1 missense (no disease association, but the paper suggests this could be responsible for the autism phenotype- KO mice have abnormal learning behaviour).
Sources: Literature
Genetic Epilepsy v0.1854 RNH1 Ain Roesley Classified gene: RNH1 as Green List (high evidence)
Genetic Epilepsy v0.1854 RNH1 Ain Roesley Gene: rnh1 has been classified as Green List (High Evidence).
Mendeliome v1.907 UNC79 Elena Savva Classified gene: UNC79 as Green List (high evidence)
Mendeliome v1.907 UNC79 Elena Savva Gene: unc79 has been classified as Green List (High Evidence).
Mendeliome v1.906 NSUN6 Michelle Torres gene: NSUN6 was added
gene: NSUN6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NSUN6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSUN6 were set to 37226891
Phenotypes for gene: NSUN6 were set to neurodevelopmental disorder MONDO:0700092, NSUN6-related
Review for gene: NSUN6 was set to AMBER
Added comment: Three unrelated consanguineous families with developmental delay, intellectual disability, motor delay, and behavioral anomalies. WES detected homozygous variants:
- p.(Leu9Glufs*3): even though authors say is is predicted to cause NMD, it actually is NMD escape. No further studies were performed. A deceased affected sibling and parents were NOT tested.
- p.(Asp323Asn): Shown to result in a misfolded protein. Methylation assay showed mutant could not catalyze m5C deposition in transcribed tRNACys and tRNAThr substrates in vitro. One of the parents and both unaffected siblings were shown to be carriers.
- p.(Glu441Profs*15): truncation (full protein is 470aa) which would result in loss of residues involved in recognition and methylation. Shown to result in a misfolded protein. Parents were shown carriers.
Sources: Literature
Genetic Epilepsy v0.1854 RNH1 Ain Roesley Publications for gene: RNH1 were set to PMID: 36935417; 37191094
Joubert syndrome and other neurological ciliopathies v1.27 TOPORS Zornitza Stark Phenotypes for gene: TOPORS were changed from Joubert syndrome, MONDO:0018772, TOPORS-related to Joubert syndrome, MONDO:0018772, TOPORS-related
Regression v0.525 RNH1 Dean Phelan reviewed gene: RNH1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37191094; Phenotypes: encephalopathy, acute, infection-induced (MONDO:0000166), RNH1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v1.26 TOPORS Zornitza Stark Marked gene: TOPORS as ready
Joubert syndrome and other neurological ciliopathies v1.26 TOPORS Zornitza Stark Gene: topors has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v1.26 TOPORS Zornitza Stark Tag founder tag was added to gene: TOPORS.
Genetic Epilepsy v0.1854 RNH1 Ain Roesley Classified gene: RNH1 as Green List (high evidence)
Genetic Epilepsy v0.1854 RNH1 Ain Roesley Gene: rnh1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1854 RNH1 Ain Roesley Publications for gene: RNH1 were set to PMID: 36935417; 37191094
Joubert syndrome and other neurological ciliopathies v1.26 TOPORS Zornitza Stark Phenotypes for gene: TOPORS were changed from macrocephaly; hypertelorism; down-slanting palpebral fissures; ptosis; polydactyly; respiratory failure; severe developmental delay to Joubert syndrome, MONDO:0018772, TOPORS-related
Intellectual disability syndromic and non-syndromic v0.5239 NSUN6 Michelle Torres gene: NSUN6 was added
gene: NSUN6 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NSUN6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSUN6 were set to 37226891
Phenotypes for gene: NSUN6 were set to neurodevelopmental disorder MONDO:0700092, NSUN6-related
Review for gene: NSUN6 was set to AMBER
Added comment: Three unrelated consanguineous families with developmental delay, intellectual disability, motor delay, and behavioral anomalies. WES detected homozygous variants:
- p.(Leu9Glufs*3): even though authors say is is predicted to cause NMD, it actually is NMD escape. No further studies were performed. A deceased affected sibling and parents were NOT tested.
- p.(Asp323Asn): Shown to result in a misfolded protein. Methylation assay showed mutant could not catalyze m5C deposition in transcribed tRNACys and tRNAThr substrates in vitro. One of the parents and both unaffected siblings were shown to be carriers.
- p.(Glu441Profs*15): truncation (full protein is 470aa) which would result in loss of residues involved in recognition and methylation. Shown to result in a misfolded protein. Parents were shown carriers.
Sources: Literature
Genetic Epilepsy v0.1853 RNH1 Ain Roesley Publications for gene: RNH1 were set to PMID: 36935417
Joubert syndrome and other neurological ciliopathies v1.25 TOPORS Zornitza Stark Classified gene: TOPORS as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v1.25 TOPORS Zornitza Stark Gene: topors has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1853 U2AF2 Elena Savva Phenotypes for gene: U2AF2 were changed from Neurodevelopmental disorder, U2AF2-related (MONDO:0700092) to Neurodevelopmental disorder, U2AF2-related (MONDO:0700092)
Genetic Epilepsy v0.1853 UNC79 Krithika Murali edited their review of gene: UNC79: Changed phenotypes: Neurodevelopmental disorder - MONDO:0700092
Mendeliome v1.906 HMGCR Naomi Baker reviewed gene: HMGCR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37167966, 36745799; Phenotypes: autosomal recessive limb-girdle muscular dystrophy (MONDO: 0015152), HMGCR-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1853 RNH1 Ain Roesley Phenotypes for gene: RNH1 were changed from Neurodevelopmental disorder, MONDO:0700092, RNH1-related to Neurodevelopmental disorder, MONDO:0700092, RNH1-related; encephalopathy, acute, infection-induced (MONDO:0000166), RNH1-related
Genetic Epilepsy v0.1853 U2AF2 Elena Savva Phenotypes for gene: U2AF2 were changed from Neurodevelopmental disorder, U2AF2-related (MONDO:0700092) to Neurodevelopmental disorder, U2AF2-related (MONDO:0700092)
Joubert syndrome and other neurological ciliopathies v1.24 TOPORS Hazel Phillimore changed review comment from: Homozygous c.29C > A; p.(Pro10Gln)) was identified in one proband with Joubert syndrome, of Dominican descent. Two other probands have been previously reported of Dominican descent with the ciliopathy oral-facial-digital syndrome by the same authors (PMID: 34132027; Strong, A, et al. (2021) American Journal of Medical Genetics. Part A, 185(8):2409–2416.
Clinical overlap between these phenotypes; therefore, the authors are proposing this as a candidate for Joubert syndrome.
Regions of homozygosity found in these three probands.
Appears to be a founder variant in individuals of Dominican descent. Query of the Mount Sinai BioMebiobank, which includes 1880 individuals of Dominican ancestry, showed 20 heterozygotes (0 homozygotes) and supports a high carrier frequency of the TOPORS p.(Pro10Gln) variant in individuals of Dominican descent.
This is in contrast to 9/152,230 in GnomAD v3.1; allele frequency 0.00005912). Four of these individuals are of African/African-American descent (4/41468; allele frequency 0.00009646) and five are of Latino/Admixed American ancestry (5/15292; allele frequency 0.00032697).

Sources: Literature; to: Homozygous c.29C > A; p.(Pro10Gln)) was identified in one proband with Joubert syndrome, of Dominican descent. Two other probands have been previously reported of Dominican descent with the ciliopathy oral-facial-digital syndrome by the same authors (PMID: 34132027; Strong, A, et al. (2021) American Journal of Medical Genetics. Part A, 185(8):2409–2416.
Clinical overlap between these phenotypes; therefore, the authors are proposing this as a candidate for Joubert syndrome.
Regions of homozygosity on chromosome 9 that includes the TOPORS gene was found in these three probands.
Appears to be a founder variant in individuals of Dominican descent. Query of the Mount Sinai BioMebiobank, which includes 1880 individuals of Dominican ancestry, showed 20 heterozygotes (0 homozygotes) and supports a high carrier frequency of the TOPORS p.(Pro10Gln) variant in individuals of Dominican descent.
This is in contrast to 9/152,230 in GnomAD v3.1; allele frequency 0.00005912). Four of these individuals are of African/African-American descent (4/41468; allele frequency 0.00009646) and five are of Latino/Admixed American ancestry (5/15292; allele frequency 0.00032697).

Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5239 UNC79 Krithika Murali edited their review of gene: UNC79: Changed phenotypes: Neurodevelopmental disorderMONDO:0700092
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.145 HMGCR Naomi Baker gene: HMGCR was added
gene: HMGCR was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for gene: HMGCR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMGCR were set to PMID: 37167966; 36745799
Phenotypes for gene: HMGCR were set to autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152), HMGCR-related
Review for gene: HMGCR was set to GREEN
Added comment: PMID: 37167966 reports nine affected individuals from five unrelated families with hypomorphic biallelic variants. Clinical presentations ranges from 4 months to 10 years, and included hydrops, delayed delayed motor milestones, prominent calves, and neck weakness. Seven missense identified, one in-frame deletion and one non-canonical splice variant. Functional studies of three missense variants demonstrated reduced exhibit significant enzymatic activity impairment relative to wild-type (WT) HMGCR protein.

PMID: 36745799 also reports a homozygous loss-of-function missense variant.
Sources: Literature
Genetic Epilepsy v0.1853 U2AF2 Elena Savva Publications for gene: U2AF2 were set to 34112922; 37092751; 36747105; 37134193
Mendeliome v1.906 UNC79 Krithika Murali gene: UNC79 was added
gene: UNC79 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UNC79 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UNC79 were set to PMID:37183800
Phenotypes for gene: UNC79 were set to Neurodevelopmental disorderMONDO:0700092
Review for gene: UNC79 was set to AMBER
Added comment: PMID:37183800 Bayat et al 2023 report 6 unrelated patients with heterozygous NMD-predicted LoF variants in UNC79 - x1 canonical splice site variant, x5 nonsense/frameshift. 5 were confirmed de novo, 1 not identified in mother - father unavailable for testing. All variants absent in gnomAD and v2 pLI score for UNC79 is 1.

Patients with UNC79 variants were identified through GeneMatcher or an international network of Epilepsy and Genetics departments. x1 patient underwent duo exome sequencing, remaining had trio exome sequencing - no other causative variants identified.

Phenotypic features included:
- 4/6 autistic features
- 5/6 patients mild-moderate ID
- 4/6 behavioural issues (aggression, stereotypies)
- 4/6 epilepsy (focal to bilateral tonic-clonic seizures)
- 5/6 hypotonia

unc79 knockdown drosophila flies exhibited significantly higher rate of seizure-like behaviour than controls. unc79 haploinsufficiency shown to lead to significant reduction in protein levels of both unc79 and unc80 in mouse brains. Unc79 haploinsufficiency associated with deficiency in hippocampal-dependent learning and memory in mice.

Authors have reviewed their own evidence in relation to the gene-disease criteria detailed by Strande et al 2017 and note that their clinical and experimental data provides moderate-level evidence supporting the association between UNC79 and a neurodevelopment disorder including ASD.

Amber association favoured due to clinical phenotypic range reported between affected individuals and their lack of specificity.
Sources: Literature
Callosome v0.491 U2AF2 Elena Savva Classified gene: U2AF2 as Amber List (moderate evidence)
Callosome v0.491 U2AF2 Elena Savva Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1853 U2AF2 Elena Savva Phenotypes for gene: U2AF2 were changed from Neurodevelopmental disorder, U2AF2-related (MONDO:0700092) to Neurodevelopmental disorder, U2AF2-related (MONDO:0700092)
Callosome v0.490 U2AF2 Elena Savva Classified gene: U2AF2 as Amber List (moderate evidence)
Callosome v0.490 U2AF2 Elena Savva Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1852 U2AF2 Elena Savva Phenotypes for gene: U2AF2 were changed from Neurodevelopmental disorder MONDO:0700092, MMGT1-related to Neurodevelopmental disorder, U2AF2-related (MONDO:0700092)
Joubert syndrome and other neurological ciliopathies v1.24 TOPORS Hazel Phillimore changed review comment from: Homozygous c.29C > A; p.(Pro10Gln)) was identified in one proband with Joubert syndrome, of Dominican descent. Two other probands have been previously reported of Dominican descent with the ciliopathy oral-facial-digital syndrome by the same authors (PMID: 34132027; Strong, A, et al. (2021) American Journal of Medical Genetics. Part A, 185(8):2409–2416.
Clinical overlap between these phenotypes; therefore, the authors are proposing this as a candidate for Joubert syndrome.
Regions of homozygosity found in these three probands.
Appears to be a founder variant in individuals of Dominican descent. Query of the Mount Sinai BioMebiobank, which includes 1880 individuals of Dominican ancestry, showed 20 heterozygotes (0 homozygotes) and supports a high carrier frequency of the TOPORS p.(Pro10Gln) variant in individuals of Dominican descent.
This is in contrast to 9/152,230 in GnomAD v3.1; allele frequency 0.00005912). Four of these individuals are of African/African-American descent (4/41468; allele frequency 0.00009646) and five are of Latino/Admixed American ancestry (5/15292; allele frequency 0.00032697).

Sources: Literature; to: Homozygous c.29C > A; p.(Pro10Gln)) was identified in one proband with Joubert syndrome, of Dominican descent. Two other probands have been previously reported of Dominican descent with the ciliopathy oral-facial-digital syndrome by the same authors (PMID: 34132027; Strong, A, et al. (2021) American Journal of Medical Genetics. Part A, 185(8):2409–2416.
Clinical overlap between these phenotypes; therefore, the authors are proposing this as a candidate for Joubert syndrome.
Regions of homozygosity found in these three probands.
Appears to be a founder variant in individuals of Dominican descent. Query of the Mount Sinai BioMebiobank, which includes 1880 individuals of Dominican ancestry, showed 20 heterozygotes (0 homozygotes) and supports a high carrier frequency of the TOPORS p.(Pro10Gln) variant in individuals of Dominican descent.
This is in contrast to 9/152,230 in GnomAD v3.1; allele frequency 0.00005912). Four of these individuals are of African/African-American descent (4/41468; allele frequency 0.00009646) and five are of Latino/Admixed American ancestry (5/15292; allele frequency 0.00032697).

Sources: Literature
Joubert syndrome and other neurological ciliopathies v1.24 TOPORS Hazel Phillimore changed review comment from: Homozygous c.29C > A; p.(Pro10Gln)) was identified in one proband with Joubert syndrome, of Dominican descent. Two other probands have been previously reported of Dominican descent with the ciliopathy oral-facial-digital syndrome by the same authors (PMID: 34132027; Strong, A, et al. (2021) American Journal of Medical Genetics. Part A, 185(8):2409–2416.
Clinical overlap between these phenotypes; therefore, the authors are proposing this as a candidate for Joubert syndrome.
Regions of homozygosity found in these three probands.
Appears to be a founder variant in individuals of Dominican descent. Query of the Mount Sinai BioMebiobank, which includes 1880 individuals of Dominican ancestry, showed 20 heterozygotes ) ) homozygotes) and supports a high carrier frequency of the TOPORS p.(Pro10Gln) variant in individuals of Dominican descent.
This is in contrast to 9/152,230 in GnomAD v3.1; allele frequency 0.00005912). Four of these individuals are of African/African-American descent (4/41468; allele frequency 0.00009646) and five are of Latino/Admixed American ancestry (5/15292; allele frequency 0.00032697).

Sources: Literature; to: Homozygous c.29C > A; p.(Pro10Gln)) was identified in one proband with Joubert syndrome, of Dominican descent. Two other probands have been previously reported of Dominican descent with the ciliopathy oral-facial-digital syndrome by the same authors (PMID: 34132027; Strong, A, et al. (2021) American Journal of Medical Genetics. Part A, 185(8):2409–2416.
Clinical overlap between these phenotypes; therefore, the authors are proposing this as a candidate for Joubert syndrome.
Regions of homozygosity found in these three probands.
Appears to be a founder variant in individuals of Dominican descent. Query of the Mount Sinai BioMebiobank, which includes 1880 individuals of Dominican ancestry, showed 20 heterozygotes (0 homozygotes) and supports a high carrier frequency of the TOPORS p.(Pro10Gln) variant in individuals of Dominican descent.
This is in contrast to 9/152,230 in GnomAD v3.1; allele frequency 0.00005912). Four of these individuals are of African/African-American descent (4/41468; allele frequency 0.00009646) and five are of Latino/Admixed American ancestry (5/15292; allele frequency 0.00032697).

Sources: Literature
Callosome v0.490 U2AF2 Elena Savva Classified gene: U2AF2 as Amber List (moderate evidence)
Callosome v0.490 U2AF2 Elena Savva Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Hydrops fetalis v0.302 NPR1 Zornitza Stark Marked gene: NPR1 as ready
Hydrops fetalis v0.302 NPR1 Zornitza Stark Gene: npr1 has been classified as Red List (Low Evidence).
Mendeliome v1.906 U2AF2 Elena Savva Publications for gene: U2AF2 were set to 34112922; 37092751; 36747105; 37134193
Joubert syndrome and other neurological ciliopathies v1.24 TOPORS Hazel Phillimore changed review comment from: Homozygous c.29C > A; p.(Pro10Gln)) was identified in one proband with Joubert syndrome, of Dominican descent. Two other probands have been previously reported of Dominican descent with the ciliopathy oral-facial-digital syndrome by the same authors (PMID: 34132027; Strong, A, et al. (2021) American Journal of Medical Genetics. Part A, 185(8):2409–2416.
Clinical overlap between these phenotypes; therefore, the authors are proposing this as a candidate for Joubert syndrome.
Appears to be a founder variant in individuals of Dominican descent. Query of the Mount Sinai BioMebiobank, which includes 1880 individuals of Dominican ancestry, supports a high carrier frequency of the TOPORS p.(Pro10Gln) variant in individuals of Dominican descent. Regions of homozygosity found in these three probands.
Sources: Literature; to: Homozygous c.29C > A; p.(Pro10Gln)) was identified in one proband with Joubert syndrome, of Dominican descent. Two other probands have been previously reported of Dominican descent with the ciliopathy oral-facial-digital syndrome by the same authors (PMID: 34132027; Strong, A, et al. (2021) American Journal of Medical Genetics. Part A, 185(8):2409–2416.
Clinical overlap between these phenotypes; therefore, the authors are proposing this as a candidate for Joubert syndrome.
Regions of homozygosity found in these three probands.
Appears to be a founder variant in individuals of Dominican descent. Query of the Mount Sinai BioMebiobank, which includes 1880 individuals of Dominican ancestry, showed 20 heterozygotes ) ) homozygotes) and supports a high carrier frequency of the TOPORS p.(Pro10Gln) variant in individuals of Dominican descent.
This is in contrast to 9/152,230 in GnomAD v3.1; allele frequency 0.00005912). Four of these individuals are of African/African-American descent (4/41468; allele frequency 0.00009646) and five are of Latino/Admixed American ancestry (5/15292; allele frequency 0.00032697).

Sources: Literature
Mendeliome v1.905 U2AF2 Elena Savva Publications for gene: U2AF2 were set to 33057194
Intellectual disability syndromic and non-syndromic v0.5239 UNC79 Krithika Murali gene: UNC79 was added
gene: UNC79 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: UNC79 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UNC79 were set to PMID:37183800
Phenotypes for gene: UNC79 were set to Complex neurodevelopmental disorder - MONDO:0100038
Review for gene: UNC79 was set to AMBER
Added comment: PMID:37183800 Bayat et al 2023 report 6 unrelated patients with heterozygous NMD-predicted LoF variants in UNC79 - x1 canonical splice site variant, x5 nonsense/frameshift. 5 were confirmed de novo, 1 not identified in mother - father unavailable for testing. All variants absent in gnomAD and v2 pLI score for UNC79 is 1.

Patients with UNC79 variants were identified through GeneMatcher or an international network of Epilepsy and Genetics departments. x1 patient underwent duo exome sequencing, remaining had trio exome sequencing - no other causative variants identified.

Phenotypic features included:
- 4/6 autistic features
- 5/6 patients mild-moderate ID
- 4/6 behavioural issues (aggression, stereotypies)
- 4/6 epilepsy (focal to bilateral tonic-clonic seizures)
- 5/6 hypotonia

unc79 knockdown drosophila flies exhibited significantly higher rate of seizure-like behaviour than controls. unc79 haploinsufficiency shown to lead to significant reduction in protein levels of both unc79 and unc80 in mouse brains. Unc79 haploinsufficiency associated with deficiency in hippocampal-dependent learning and memory in mice.

Authors have reviewed their own evidence in relation to the gene-disease criteria detailed by Strande et al 2017 and note that their clinical and experimental data provides moderate-level evidence supporting the association between UNC79 and a neurodevelopment disorder including ASD.

Amber association favoured due to clinical phenotypic range reported between affected individuals and their lack of specificity.
Sources: Literature
Mendeliome v1.905 U2AF2 Elena Savva Classified gene: U2AF2 as Green List (high evidence)
Mendeliome v1.905 U2AF2 Elena Savva Gene: u2af2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1852 U2AF2 Elena Savva Publications for gene: U2AF2 were set to 34112922
Leukodystrophy - paediatric v0.287 U2AF2 Elena Savva Classified gene: U2AF2 as Red List (low evidence)
Leukodystrophy - paediatric v0.287 U2AF2 Elena Savva Gene: u2af2 has been classified as Red List (Low Evidence).
Hydrocephalus_Ventriculomegaly v0.119 KIF26A Belinda Chong gene: KIF26A was added
gene: KIF26A was added to Hydrocephalus_Ventriculomegaly. Sources: Literature
Mode of inheritance for gene: KIF26A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF26A were set to 36564622
Phenotypes for gene: KIF26A were set to Cortical dysplasia, complex, with other brain malformations 11, MIM# 620156
Review for gene: KIF26A was set to GREEN
gene: KIF26A was marked as current diagnostic
Added comment: Five individuals from two families each with a different homozygous truncating variant in KIF26A segregating with profound ENS dysfunction that manifested clinically like Hirschsprung’s disease despite normal ganglionosis. Moreover, they all have neurological involvement with brain malformations ranging from ventriculomegaly to severe congenital hydrocephalus in two siblings who died early in life. Clinically, they displayed developmental delay and, in the longest surviving individual, spastic paraplegia.
Sources: Literature
Callosome v0.489 U2AF2 Elena Savva Marked gene: U2AF2 as ready
Callosome v0.489 U2AF2 Elena Savva Gene: u2af2 has been removed from the panel.
Leukodystrophy - paediatric v0.286 U2AF2 Elena Savva Marked gene: U2AF2 as ready
Leukodystrophy - paediatric v0.286 U2AF2 Elena Savva Gene: u2af2 has been removed from the panel.
Hirschsprung disease v0.24 KIF26A Belinda Chong changed review comment from: Two unrelated families each segregating a different homozygous truncating variant in KIF26A with a unique constellation of severe megacolon that resembles Hirschsprung’s disease but lacks aganglionosis as well as brain malformations that range from severe to mild. The intestinal phenotype bears a striking resemblance to that observed in Kif26a−/− mice where KIF26A deficiency was found to cause abnormal GDNF-Ret signaling resulting in failure to establish normal neuronal networks despite myenteric neuronal hyperplasia.
Sources: Literature; to: Five individuals from two families each with a different homozygous truncating variant in KIF26A segregating with profound ENS dysfunction that manifested clinically like Hirschsprung’s disease despite normal ganglionosis. Moreover, they all have neurological involvement with brain malformations ranging from ventriculomegaly to severe congenital hydrocephalus in two siblings who died early in life. Clinically, they displayed developmental delay and, in the longest surviving individual, spastic paraplegia.
Hydrops fetalis v0.302 NPR1 Zornitza Stark Classified gene: NPR1 as Red List (low evidence)
Genetic Epilepsy v0.1852 U2AF2 Elena Savva Classified gene: U2AF2 as Green List (high evidence)
Hydrops fetalis v0.302 NPR1 Zornitza Stark Gene: npr1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1852 U2AF2 Elena Savva Gene: u2af2 has been classified as Green List (High Evidence).
Hydrops fetalis v0.302 BICD2 Ain Roesley Classified gene: BICD2 as Amber List (moderate evidence)
Hydrops fetalis v0.302 BICD2 Ain Roesley Gene: bicd2 has been classified as Amber List (Moderate Evidence).
Hydrops fetalis v0.301 BICD2 Ee Ming Wong changed review comment from: - Fetus with severe hydrops fetalis (hydrops, hypoplastic lungs, fixed flexion deformities). Neuropathology suggests congenital myopathy or dystrophic process
- Confirmed to be de novo for a missense variant in BICD2
- Authors referenced a previous publication as additional evidence for BICD2 association with hydrops (PMID: 28635954). However, based on phenotypic information provided by Storbeck et al (2017) the reported individual did not have hydrops.
Sources: Literature; to: - Fetus with severe hydrops fetalis (hydrops, hypoplastic lungs, fixed flexion deformities). Neuropathology suggests congenital myopathy or dystrophic process
- Confirmed to be de novo for a missense variant in BICD2
- Authors referenced a previous publication as additional evidence for BICD2 association with hydrops (PMID: 28635954). However, based on phenotypic information provided by Storbeck et al (2017) the reported individual was not determined to have hydrops.
Sources: Literature
Genetic Epilepsy v0.1852 U2AF2 Elena Savva Classified gene: U2AF2 as Green List (high evidence)
Genetic Epilepsy v0.1852 U2AF2 Elena Savva Gene: u2af2 has been classified as Green List (High Evidence).
Hydrops fetalis v0.301 BICD2 Ain Roesley Classified gene: BICD2 as Amber List (moderate evidence)
Hydrops fetalis v0.301 BICD2 Ain Roesley Gene: bicd2 has been classified as Amber List (Moderate Evidence).
Hydrops fetalis v0.300 BICD2 Ain Roesley Marked gene: BICD2 as ready
Hydrops fetalis v0.300 BICD2 Ain Roesley Gene: bicd2 has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.5239 ACBD6 Elena Savva Classified gene: ACBD6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5239 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1851 UNC79 Krithika Murali gene: UNC79 was added
gene: UNC79 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: UNC79 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UNC79 were set to PMID:37183800
Phenotypes for gene: UNC79 were set to Complex neurodevelopmental disorder - MONDO:0100038
Review for gene: UNC79 was set to AMBER
Added comment: PMID:37183800 Bayat et al 2023 report 6 unrelated patients with heterozygous NMD-predicted LoF variants in UNC79 - x1 canonical splice site variant, x5 nonsense/frameshift. 5 were confirmed de novo, 1 not identified in mother - father unavailable for testing. All variants absent in gnomAD and v2 pLI score for UNC79 is 1.

Patients with UNC79 variants were identified through GeneMatcher or an international network of Epilepsy and Genetics departments. x1 patient underwent duo exome sequencing, remaining had trio exome sequencing - no other causative variants identified.

Phenotypic features included:
- 4/6 autistic features
- 5/6 patients mild-moderate ID
- 4/6 behavioural issues (aggression, stereotypies)
- 4/6 epilepsy (focal to bilateral tonic-clonic seizures)
- 5/6 hypotonia

unc79 knockdown drosophila flies exhibited significantly higher rate of seizure-like behaviour than controls. unc79 haploinsufficiency shown to lead to significant reduction in protein levels of both unc79 and unc80 in mouse brains anddeficiency in hippocampal-dependent learning and memory in mice.

Authors have reviewed their own evidence in relation to the gene-disease criteria detailed by Strande et al 2017 and note that their clinical and experimental data provides moderate-level evidence supporting the association between UNC79 and a neurodevelopment disorder
including ASD.

Evidence emerging is promising, however Amber association favoured due to clinical phenotypic range reported between affected individuals and their lack of specificity.
Sources: Literature
Mendeliome v1.904 NPR1 Zornitza Stark Marked gene: NPR1 as ready
Mendeliome v1.904 NPR1 Zornitza Stark Gene: npr1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5237 ACBD6 Elena Savva Classified gene: ACBD6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5237 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Mendeliome v1.904 NPR1 Zornitza Stark Classified gene: NPR1 as Green List (high evidence)
Mendeliome v1.904 NPR1 Zornitza Stark Gene: npr1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5236 POU3F2 Ain Roesley Classified gene: POU3F2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5236 POU3F2 Ain Roesley Gene: pou3f2 has been classified as Green List (High Evidence).
Hypertension and Aldosterone disorders v1.14 NPR1 Zornitza Stark Marked gene: NPR1 as ready
Hypertension and Aldosterone disorders v1.14 NPR1 Zornitza Stark Gene: npr1 has been classified as Green List (High Evidence).
Mendeliome v1.903 MRPL50 Anna Ritchie gene: MRPL50 was added
gene: MRPL50 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MRPL50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPL50 were set to PMID: 37148394
Phenotypes for gene: MRPL50 were set to Mitochondrial disease, MONDO: 004470, MRPL50-related
Added comment: A homozygous missense variant (c.335T>A; p.Val112Asp) shared by twin sisters presenting with premature ovarian insufficiency, bilateral high-frequency sensorineural hearing loss, kidney and heart dysfunction.
Quantitative proteomics data demonstrated a significant reduction in abundance of MRPL50 protein when compared with controls.
Patient fibroblasts have a mild but significant decrease in the abundance of mitochondrial complex I. This data supports a biochemical phenotype associated with MRPL50 variants.
Knockdown/knockout of mRpL50 in Drosophila, resulted abnormal ovarian development.
Sources: Literature
Hypertension and Aldosterone disorders v1.14 NPR1 Zornitza Stark Classified gene: NPR1 as Green List (high evidence)
Hypertension and Aldosterone disorders v1.14 NPR1 Zornitza Stark Gene: npr1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.310 MRPL50 Anna Ritchie gene: MRPL50 was added
gene: MRPL50 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature
Mode of inheritance for gene: MRPL50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPL50 were set to PMID: 37148394
Phenotypes for gene: MRPL50 were set to Mitochondrial disease, MONDO: 004470, MRPL50-related
Review for gene: MRPL50 was set to AMBER
Added comment: A homozygous missense variant (c.335T>A; p.Val112Asp) shared by twin sisters presenting with premature ovarian insufficiency, bilateral high-frequency sensorineural hearing loss, kidney and heart dysfunction.
Quantitative proteomics data demonstrated a significant reduction in abundance of MRPL50 protein when compared with controls.
Patient fibroblasts have a mild but significant decrease in the abundance of mitochondrial complex I. This data supports a biochemical phenotype associated with MRPL50 variants.
Knockdown/knockout of mRpL50 in Drosophila, resulted abnormal ovarian development.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5236 U2AF2 Elena Savva Phenotypes for gene: U2AF2 were changed from Neurodevelopmental disorder, U2AF2-related (MONDO:0700092) to Neurodevelopmental disorder, U2AF2-related (MONDO:0700092)
Genetic Epilepsy v0.1851 ANK2 Karina Sandoval gene: ANK2 was added
gene: ANK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ANK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANK2 were set to PMID:37195288
Phenotypes for gene: ANK2 were set to Epilepsy, MONDO:0005027, Complex neurodevelopmental disorder, MONDO:0100038
Review for gene: ANK2 was set to GREEN
Added comment: Paper included 12 individuals with LoF variants. 11 were confirmed de novo. Paper found broad NND comprising of ID, ASD and early onset epilepsy, both mild and severed ID & epilepsy.
Variants included 4 nonsense, 3 fs, 3 canonical splice, and 2 partial gene dels.
Early childhood epilepsy was reported in 7 of 12 patients. 4 patients had neonatal onset epilepsy. 1 patient had bilateral tonic-clinic seizures at 3 years of age. Another patient had focal epilepsy with focal motor seizures.
Sources: Literature
Mitochondrial disease v0.874 MRPL50 Anna Ritchie gene: MRPL50 was added
gene: MRPL50 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: MRPL50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPL50 were set to PMID: 37148394
Phenotypes for gene: MRPL50 were set to Mitochondrial disease, MONDO: 004470, MRPL50-related
Review for gene: MRPL50 was set to AMBER
Added comment: A homozygous missense variant (c.335T>A; p.Val112Asp) shared by twin sisters presenting with premature ovarian insufficiency, bilateral high-frequency sensorineural hearing loss, kidney and heart dysfunction.
Quantitative proteomics data demonstrated a significant reduction in abundance of MRPL50 protein when compared with controls.
Patient fibroblasts have a mild but significant decrease in the abundance of mitochondrial complex I. This data supports a biochemical phenotype associated with MRPL50 variants.
Knockdown/knockout of mRpL50 in Drosophila, resulted abnormal ovarian development.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5238 POU3F2 Ain Roesley Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related
Intellectual disability syndromic and non-syndromic v0.5238 ACBD6 Elena Savva Marked gene: ACBD6 as ready
Intellectual disability syndromic and non-syndromic v0.5238 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5238 MCM6 Zornitza Stark Classified gene: MCM6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5238 MCM6 Zornitza Stark Gene: mcm6 has been classified as Green List (High Evidence).
Hirschsprung disease v0.24 KIF26A Belinda Chong gene: KIF26A was added
gene: KIF26A was added to Hirschsprung disease. Sources: Literature
Mode of inheritance for gene: KIF26A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF26A were set to 36564622
Phenotypes for gene: KIF26A were set to Cortical dysplasia, complex, with other brain malformations 11, MIM# 620156
Review for gene: KIF26A was set to GREEN
gene: KIF26A was marked as current diagnostic
Added comment: Two unrelated families each segregating a different homozygous truncating variant in KIF26A with a unique constellation of severe megacolon that resembles Hirschsprung’s disease but lacks aganglionosis as well as brain malformations that range from severe to mild. The intestinal phenotype bears a striking resemblance to that observed in Kif26a−/− mice where KIF26A deficiency was found to cause abnormal GDNF-Ret signaling resulting in failure to establish normal neuronal networks despite myenteric neuronal hyperplasia.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5238 ACBD6 Elena Savva Classified gene: ACBD6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5238 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5237 POU3F2 Ain Roesley Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related
Severe early-onset obesity v1.8 ACBD6 Lucy Spencer gene: ACBD6 was added
gene: ACBD6 was added to Severe early-onset obesity. Sources: Literature
Mode of inheritance for gene: ACBD6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACBD6 were set to 36457943; 21937992; 35446914
Phenotypes for gene: ACBD6 were set to Neurodevelopmental disorder (MONDO#0700092), ACBD6-related
Review for gene: ACBD6 was set to AMBER
Added comment: PMID: 36457943
2 siblings with a neurodevelopmental disorder: severely delayed development, obesity, pancytopenia, diabetes, liver cirrhosis, intravertebral disc herniation, mild brain atrophy. Consanguineous family both siblings found to have a homozygous frameshift.

This paper also mentioned 3 other reported variants in 6 individuals (only 3 unrelated) all homozygous, 2 frameshift, 1 canonical splice. All reported to have a neurodevelopmental disorder, some with limited information but one family also has obesity, spasticity, and dysmorphism. PMIDs: 21937992, 35446914
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5237 U2AF2 Elena Savva Phenotypes for gene: U2AF2 were changed from Neurodevelopmental disorder, U2AF2-related (MONDO:0700092) to Neurodevelopmental disorder, U2AF2-related (MONDO:0700092)
Intellectual disability syndromic and non-syndromic v0.5236 MCM6 Zornitza Stark Classified gene: MCM6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5236 MCM6 Zornitza Stark Gene: mcm6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5236 MCM6 Zornitza Stark Classified gene: MCM6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5236 MCM6 Zornitza Stark Gene: mcm6 has been classified as Green List (High Evidence).
Mendeliome v1.903 POU3F2 Ain Roesley Marked gene: POU3F2 as ready
Mendeliome v1.903 POU3F2 Ain Roesley Gene: pou3f2 has been classified as Green List (High Evidence).
Mendeliome v1.903 ACBD6 Elena Savva Marked gene: ACBD6 as ready
Mendeliome v1.903 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5237 POU3F2 Ain Roesley Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related
Mendeliome v1.903 ACBD6 Elena Savva Marked gene: ACBD6 as ready
Mendeliome v1.903 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Mendeliome v1.903 POU3F2 Ain Roesley Classified gene: POU3F2 as Green List (high evidence)
Mendeliome v1.903 POU3F2 Ain Roesley Gene: pou3f2 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v1.24 TOPORS Hazel Phillimore gene: TOPORS was added
gene: TOPORS was added to Joubert syndrome and other neurological ciliopathies. Sources: Literature
Mode of inheritance for gene: TOPORS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOPORS were set to PMID: 37227088; 34132027
Phenotypes for gene: TOPORS were set to macrocephaly; hypertelorism; down-slanting palpebral fissures; ptosis; polydactyly; respiratory failure; severe developmental delay
Review for gene: TOPORS was set to AMBER
Added comment: Homozygous c.29C > A; p.(Pro10Gln)) was identified in one proband with Joubert syndrome, of Dominican descent. Two other probands have been previously reported of Dominican descent with the ciliopathy oral-facial-digital syndrome by the same authors (PMID: 34132027; Strong, A, et al. (2021) American Journal of Medical Genetics. Part A, 185(8):2409–2416.
Clinical overlap between these phenotypes; therefore, the authors are proposing this as a candidate for Joubert syndrome.
Appears to be a founder variant in individuals of Dominican descent. Query of the Mount Sinai BioMebiobank, which includes 1880 individuals of Dominican ancestry, supports a high carrier frequency of the TOPORS p.(Pro10Gln) variant in individuals of Dominican descent. Regions of homozygosity found in these three probands.
Sources: Literature
Callosome v0.489 U2AF2 Paul De Fazio gene: U2AF2 was added
gene: U2AF2 was added to Callosome. Sources: Literature
Mode of inheritance for gene: U2AF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: U2AF2 were set to 34112922; 37092751; 36747105; 37134193
Phenotypes for gene: U2AF2 were set to Neurodevelopmental disorder, U2AF2-related (MONDO:0700092)
Review for gene: U2AF2 was set to AMBER
gene: U2AF2 was marked as current diagnostic
Added comment: 4 patients with de novo missense variants reported, of which 2 had hypoplastic corpus callosum (PMID: 34112922, 36747105).
Sources: Literature
Mendeliome v1.902 ACBD6 Elena Savva Classified gene: ACBD6 as Green List (high evidence)
Mendeliome v1.902 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Mendeliome v1.902 ACBD6 Elena Savva Classified gene: ACBD6 as Green List (high evidence)
Mendeliome v1.902 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Mendeliome v1.901 ACBD6 Elena Savva Marked gene: ACBD6 as ready
Mendeliome v1.901 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5237 POU3F2 Ain Roesley Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related
Mendeliome v1.901 POU3F2 Ain Roesley Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related
Mendeliome v1.901 ACBD6 Elena Savva Classified gene: ACBD6 as Green List (high evidence)
Mendeliome v1.901 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.286 U2AF2 Paul De Fazio gene: U2AF2 was added
gene: U2AF2 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: U2AF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: U2AF2 were set to 34112922; 37092751; 36747105; 37134193
Phenotypes for gene: U2AF2 were set to Neurodevelopmental disorder, U2AF2-related (MONDO:0700092)
Review for gene: U2AF2 was set to RED
gene: U2AF2 was marked as current diagnostic
Added comment: 4 patients with de novo missense variants reported, however only one report (PMID: 37134193) of hymomyelinating leukodystrophy.
Sources: Literature
Mendeliome v1.901 MCM6 Zornitza Stark Publications for gene: MCM6 were set to
Hydrops fetalis v0.300 NPR1 Lilian Downie changed review comment from: single family (4 affected infants) with neonatal hypertension/cardiogenic shock
3/4 sibs had NT >3.5
Sources: Literature; to: single family (4 affected infants) with neonatal hypertension/cardiogenic shock
3/4 sibs had NT >3.5
a slight reduction in the expected number of homozygous
Npr1 knockout mutant mice was statistically significant and
is related to fetal hydrops observed in approximately 10% of
homozygous embryos

Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5235 POU3F2 Ain Roesley Classified gene: POU3F2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5235 POU3F2 Ain Roesley Gene: pou3f2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5236 POU3F2 Ain Roesley Marked gene: POU3F2 as ready
Intellectual disability syndromic and non-syndromic v0.5236 POU3F2 Ain Roesley Gene: pou3f2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5236 U2AF2 Elena Savva Classified gene: U2AF2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5236 U2AF2 Elena Savva Gene: u2af2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1851 RNH1 Dean Phelan reviewed gene: RNH1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37191094; Phenotypes: encephalopathy, acute, infection-induced (MONDO:0000166), RNH1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.900 MCM6 Zornitza Stark Phenotypes for gene: MCM6 were changed from Lactase persistence/nonpersistence 223100 to Neurodevelopmental disorder, MONDO:0700092, MCM6-related; Lactase persistence/nonpersistence 223100
Hydrops fetalis v0.300 BICD2 Ee Ming Wong gene: BICD2 was added
gene: BICD2 was added to Hydrops fetalis. Sources: Literature
Mode of inheritance for gene: BICD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BICD2 were set to 37173812
Phenotypes for gene: BICD2 were set to Spinal muscular atrophy, lower extremity-predominant 2B, prenatal-onset (MIM#609797)
Review for gene: BICD2 was set to AMBER
gene: BICD2 was marked as current diagnostic
Added comment: - Fetus with severe hydrops fetalis (hydrops, hypoplastic lungs, fixed flexion deformities). Neuropathology suggests congenital myopathy or dystrophic process
- Confirmed to be de novo for a missense variant in BICD2
- Authors referenced a previous publication as additional evidence for BICD2 association with hydrops (PMID: 28635954). However, based on phenotypic information provided by Storbeck et al (2017) the reported individual did not have hydrops.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5236 POU3F2 Ain Roesley Classified gene: POU3F2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5236 POU3F2 Ain Roesley Gene: pou3f2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5235 U2AF2 Elena Savva Phenotypes for gene: U2AF2 were changed from Neurodevelopmental disorder, U2AF2-related (MONDO:0700092) to Neurodevelopmental disorder, U2AF2-related (MONDO:0700092)
Microcephaly v1.207 MCM6 Zornitza Stark Classified gene: MCM6 as Amber List (moderate evidence)
Microcephaly v1.207 MCM6 Zornitza Stark Gene: mcm6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5235 U2AF2 Elena Savva Phenotypes for gene: U2AF2 were changed from Neurodevelopmental disorder MONDO:0700092, MMGT1-related to Neurodevelopmental disorder, U2AF2-related (MONDO:0700092)
Mendeliome v1.899 MCM6 Zornitza Stark Classified gene: MCM6 as Green List (high evidence)
Mendeliome v1.899 MCM6 Zornitza Stark Gene: mcm6 has been classified as Green List (High Evidence).
Microcephaly v1.206 MCM6 Zornitza Stark Marked gene: MCM6 as ready
Mendeliome v1.898 NPR1 Lilian Downie gene: NPR1 was added
gene: NPR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NPR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPR1 were set to PMID: 37080586
Phenotypes for gene: NPR1 were set to Genetic hypertension MONDO:0015512
Review for gene: NPR1 was set to GREEN
Added comment: 4 sibs with systemic hypertension in the neonatal period - presenting with cardiogenic shock, with homozygous variants (consanguineous parents), parents confirmed heterozygotes. 3/4 infants had increased NT (>3.5) in utero
RT-PCR shows dramatic reduction of RNA levels
2 sibs in a second family, normal NT and pregnancy, neonatal systematic hypertension presenting with cardiogenic shock,
Sources: Literature
Microcephaly v1.206 MCM6 Zornitza Stark Gene: mcm6 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.206 MCM6 Zornitza Stark Classified gene: MCM6 as Amber List (moderate evidence)
Microcephaly v1.206 MCM6 Zornitza Stark Gene: mcm6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5235 U2AF2 Elena Savva Publications for gene: U2AF2 were set to 33057194
Microcephaly v1.206 MCM6 Zornitza Stark Classified gene: MCM6 as Amber List (moderate evidence)
Microcephaly v1.206 MCM6 Zornitza Stark Gene: mcm6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5235 U2AF2 Elena Savva Classified gene: U2AF2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5235 U2AF2 Elena Savva Gene: u2af2 has been classified as Green List (High Evidence).
Hydrops fetalis v0.300 NPR1 Lilian Downie gene: NPR1 was added
gene: NPR1 was added to Hydrops fetalis. Sources: Literature
Mode of inheritance for gene: NPR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPR1 were set to PMID: 37080586
Phenotypes for gene: NPR1 were set to Genetic hypertension MONDO:0015512
Review for gene: NPR1 was set to RED
Added comment: single family (4 affected infants) with neonatal hypertension/cardiogenic shock
3/4 sibs had NT >3.5
Sources: Literature
Mendeliome v1.898 POU3F2 Sarah Pantaleo gene: POU3F2 was added
gene: POU3F2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POU3F2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POU3F2 were set to PMID: 37207645
Phenotypes for gene: POU3F2 were set to Autism spectrum disorder, NDD, and adolescent-onset obesity
Penetrance for gene: POU3F2 were set to unknown
Mode of pathogenicity for gene: POU3F2 was set to Other
Review for gene: POU3F2 was set to GREEN
Added comment: We associate ultra-rare variants in POU3F2, encoding a central nervous system transcription factor, with syndromic obesity and neurodevelopment delay in 12 individuals. Demonstrate variant pathogenicity through in vitro analysis. Used exome sequencing, GeneMatcher and Genomics England 100,000 Genomes Project rare disease database.

Both truncating and missense variants in over 10 individuals sharing autism spectrum disorder, NDD, and adolescent-onset obesity (may have had other features eg. CAKUT in 2 individuals, diabetes in two) . Affected individuals presented with low-to-normal birth weight and infantile feeding difficulties but developed insulin resistance and hyperplasia during childhood. With the exception of an early truncating variant, the variants showed adequate nuclear translocation but overall disturbed DNA-binding ability and promoter activation.

Variants absent from population and clinical databases. Almost all constituted putatively non-inherited de novo variants (8/10).

Functional studies provide evidence for loss of function in eight and gain of function in one obesity-associated POU3F2 variant. One variant did not impact POU3F2-promoter activation, leaving the possibility for further path-mechanisms.
Sources: Literature
Hypertension and Aldosterone disorders v1.13 NPR1 Lilian Downie gene: NPR1 was added
gene: NPR1 was added to Hypertension and Aldosterone disorders. Sources: Literature
Mode of inheritance for gene: NPR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPR1 were set to PMID: 37080586
Phenotypes for gene: NPR1 were set to Genetic hypertension MONDO:0015512
Review for gene: NPR1 was set to GREEN
Added comment: 4 sibs with systemic hypertension in the neonatal period - presenting with cardiogenic shock, with homozygous variants (consanguineous parents), parents confirmed heterozygotes. 3/4 infants had increased NT (>3.5) in utero
RT-PCR shows dramatic reduction of RNA levels
2 sibs in a second family, normal NT and pregnancy, neonatal systematic hypertension presenting with cardiogenic shock,
Sources: Literature
Mendeliome v1.898 MAP4K4 Zornitza Stark Mode of inheritance for gene: MAP4K4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.897 ACBD6 Lucy Spencer gene: ACBD6 was added
gene: ACBD6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ACBD6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACBD6 were set to 36457943; 21937992; 35446914
Phenotypes for gene: ACBD6 were set to Neurodevelopmental disorder (MONDO#0700092), ACBD6-related
Review for gene: ACBD6 was set to GREEN
Added comment: PMID: 36457943
2 siblings with a neurodevelopmental disorder: severely delayed development, obesity, pancytopenia, diabetes, liver cirrhosis, intravertebral disc herniation, mild brain atrophy. Consanguineous family both siblings found to have a homozygous frameshift.

This paper also mentioned 3 other reported variants in 6 individuals (only 3 unrelated) all homozygous, 2 frameshift, 1 canonical splice. All reported to have a neurodevelopmental disorder, some with limited information but one family also has obesity, spasticity, and dysmorphism. PMIDs: 21937992, 35446914
Sources: Literature
Mendeliome v1.897 MAP4K4 Zornitza Stark Classified gene: MAP4K4 as Green List (high evidence)
Mendeliome v1.897 MAP4K4 Zornitza Stark Gene: map4k4 has been classified as Green List (High Evidence).
Mendeliome v1.896 U2AF2 Paul De Fazio reviewed gene: U2AF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34112922, 37092751, 36747105, 37134193; Phenotypes: Neurodevelopmental disorder, U2AF2-related (MONDO:0700092); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v1.896 MAP4K4 Zornitza Stark edited their review of gene: MAP4K4: Added comment: 26 individuals from 21 families reported with Rasopathy-like phenotype, comprising ID/DD, dysmorphic features and congenital anomalies.; Changed rating: GREEN; Changed publications: 37126546; Changed phenotypes: RASopathy, MONDO:0021060, MAP4K4-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5234 ACBD6 Lucy Spencer gene: ACBD6 was added
gene: ACBD6 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ACBD6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACBD6 were set to 36457943; 21937992; 35446914
Phenotypes for gene: ACBD6 were set to Neurodevelopmental disorder (MONDO#0700092), ACBD6-related
Review for gene: ACBD6 was set to GREEN
Added comment: PMID: 36457943
2 siblings with a neurodevelopmental disorder: severely delayed development, obesity, pancytopenia, diabetes, liver cirrhosis, intravertebral disc herniation, mild brain atrophy. Consanguineous family both siblings found to have a homozygous frameshift.

This paper also mentioned 3 other reported variants in 6 individuals (only 3 unrelated) all homozygous, 2 frameshift, 1 canonical splice. All reported to have a neurodevelopmental disorder, some with limited information but one family also has obesity, spasticity, and dysmorphism. PMIDs: 21937992, 35446914
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5234 POU3F2 Sarah Pantaleo commented on gene: POU3F2: Both loss of function and gain of function demonstrated
Fetal anomalies v1.111 MAP4K4 Zornitza Stark Marked gene: MAP4K4 as ready
Fetal anomalies v1.111 MAP4K4 Zornitza Stark Gene: map4k4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5234 U2AF2 Paul De Fazio edited their review of gene: U2AF2: Changed publications: 34112922, 37092751, 36747105, 37134193
Intellectual disability syndromic and non-syndromic v0.5234 POU3F2 Sarah Pantaleo gene: POU3F2 was added
gene: POU3F2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: POU3F2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POU3F2 were set to PMID: 37207645
Phenotypes for gene: POU3F2 were set to Autism spectrum disorder, NDD, and adolescent-onset obesity
Penetrance for gene: POU3F2 were set to unknown
Mode of pathogenicity for gene: POU3F2 was set to Other
Review for gene: POU3F2 was set to GREEN
Added comment: We associate ultra-rare variants in POU3F2, encoding a central nervous system transcription factor, with syndromic obesity and neurodevelopment delay in 12 individuals. Demonstrate variant pathogenicity through in vitro analysis. Used exome sequencing, GeneMatcher and Genomics England 100,000 Genomes Project rare disease database.

Both truncating and missense variants in over 10 individuals sharing autism spectrum disorder, NDD, and adolescent-onset obesity (may have had other features eg. CAKUT in 2 individuals, diabetes in two) . Affected individuals presented with low-to-normal birth weight and infantile feeding difficulties but developed insulin resistance and hyperplasia during childhood. With the exception of an early truncating variant, the variants showed adequate nuclear translocation but overall disturbed DNA-binding ability and promoter activation.

Variants absent from population and clinical databases. Almost all constituted putatively non-inherited de novo variants (8/10).

Functional studies provide evidence for loss of function in eight and gain of function in one obesity-associated POU3F2 variant. One variant did not impact POU3F2-promoter activation, leaving the possibility for further path-mechanisms.
Sources: Literature
Genetic Epilepsy v0.1851 U2AF2 Paul De Fazio edited their review of gene: U2AF2: Changed publications: 34112922, 37092751, 36747105, 37134193
Genetic Epilepsy v0.1851 U2AF2 Paul De Fazio reviewed gene: U2AF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34112922,37092751,36747105,37134193; Phenotypes: Neurodevelopmental disorder, U2AF2-related (MONDO:0700092); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Fetal anomalies v1.111 MAP4K4 Zornitza Stark Classified gene: MAP4K4 as Green List (high evidence)
Fetal anomalies v1.111 MAP4K4 Zornitza Stark Gene: map4k4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5234 U2AF2 Paul De Fazio edited their review of gene: U2AF2: Changed rating: GREEN; Changed phenotypes: Neurodevelopmental disorder, U2AF2-related (MONDO:0700092); Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.110 MAP4K4 Zornitza Stark gene: MAP4K4 was added
gene: MAP4K4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MAP4K4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP4K4 were set to 37126546
Phenotypes for gene: MAP4K4 were set to RASopathy, MONDO:0021060, MAP4K4-related
Review for gene: MAP4K4 was set to GREEN
Added comment: 26 individuals from 21 families reported with Rasopathy-like phenotype, comprising ID/DD, dysmorphic features and congenital anomalies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5234 U2AF2 Paul De Fazio reviewed gene: U2AF2: Rating: ; Mode of pathogenicity: None; Publications: 34112922,37092751,36747105,37134193; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5234 MAP4K4 Zornitza Stark Phenotypes for gene: MAP4K4 were changed from to RASopathy, MONDO:0021060, MAP4K4-related
Mendeliome v1.896 CHRM5 Elena Savva gene: CHRM5 was added
gene: CHRM5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CHRM5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHRM5 were set to 37213061
Phenotypes for gene: CHRM5 were set to Congenital anomaly of kidney and urinary tract, (MONDO:0019719), CHRM5-related
Review for gene: CHRM5 was set to RED
Added comment: PMID: 37213061
- homozygous missense p.(Q184R) in a proband with neurogenic bladder and CAKUT. Additional features were small trabeculated urinary bladder, bilateral severe hydronephrosis, grade V VUR right, chronic kidney disease (stage 4).
- Radioligand binding experiments were inconclusive - the missense variant had no effect on receptor expression or binding affinity.
- ACh binding assay did show a 2-fold increase (borderline significant), but no effect in secondary messenger accumulation.
- Transfected CHO line showed no effect on receptor expression
- Described a mouse K/O as having a bladder overactivity

No hom PTCs in gnomAD
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5233 MAP4K4 Zornitza Stark Mode of inheritance for gene: MAP4K4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.130 CHRM5 Elena Savva gene: CHRM5 was added
gene: CHRM5 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Literature
Mode of inheritance for gene: CHRM5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHRM5 were set to 37213061
Phenotypes for gene: CHRM5 were set to Congenital anomaly of kidney and urinary tract, (MONDO:0019719), CHRM5-related
Review for gene: CHRM5 was set to RED
Added comment: PMID: 37213061
- homozygous missense p.(Q184R) in a proband with neurogenic bladder and CAKUT. Additional features were small trabeculated urinary bladder, bilateral severe hydronephrosis, grade V VUR right, chronic kidney disease (stage 4).
- Radioligand binding experiments were inconclusive - the missense variant had no effect on receptor expression or binding affinity.
- ACh binding assay did show a 2-fold increase (borderline significant), but no effect in secondary messenger accumulation.
- Transfected CHO line showed no effect on receptor expression
- Described a mouse K/O as having a bladder overactivity

No hom PTCs in gnomAD
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5233 MAP4K4 Zornitza Stark Mode of inheritance for gene: MAP4K4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.130 CHRM5 Elena Savva gene: CHRM5 was added
gene: CHRM5 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Literature
Mode of inheritance for gene: CHRM5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHRM5 were set to 37213061
Phenotypes for gene: CHRM5 were set to Congenital anomaly of kidney and urinary tract, (MONDO:0019719), CHRM5-related
Review for gene: CHRM5 was set to RED
Added comment: PMID: 37213061
- homozygous missense p.(Q184R) in a proband with neurogenic bladder and CAKUT. Additional features were small trabeculated urinary bladder, bilateral severe hydronephrosis, grade V VUR right, chronic kidney disease (stage 4).
- Radioligand binding experiments were inconclusive - the missense variant had no effect on receptor expression or binding affinity.
- ACh binding assay did show a 2-fold increase (borderline significant), but no effect in secondary messenger accumulation.
- Transfected CHO line showed no effect on receptor expression
- Described a mouse K/O as having a bladder overactivity

No hom PTCs in gnomAD
Sources: Literature
Congenital Heart Defect v0.283 MAP4K4 Zornitza Stark Marked gene: MAP4K4 as ready
Congenital Heart Defect v0.283 MAP4K4 Zornitza Stark Gene: map4k4 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.283 MAP4K4 Zornitza Stark Classified gene: MAP4K4 as Green List (high evidence)
Congenital Heart Defect v0.283 MAP4K4 Zornitza Stark Gene: map4k4 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.282 MAP4K4 Zornitza Stark gene: MAP4K4 was added
gene: MAP4K4 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: MAP4K4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP4K4 were set to 37126546
Phenotypes for gene: MAP4K4 were set to RASopathy, MONDO:0021060, MAP4K4-related
Review for gene: MAP4K4 was set to GREEN
Added comment: 26 individuals from 21 families reported with Rasopathy-like phenotype, comprising ID/DD, dysmorphic features and congenital anomalies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5232 MAP4K4 Zornitza Stark Publications for gene: MAP4K4 were set to 37126546
Intellectual disability syndromic and non-syndromic v0.5232 MAP4K4 Zornitza Stark Publications for gene: MAP4K4 were set to
Intellectual disability syndromic and non-syndromic v0.5231 MAP4K4 Zornitza Stark Classified gene: MAP4K4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5231 MAP4K4 Zornitza Stark Gene: map4k4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5230 MAP4K4 Zornitza Stark commented on gene: MAP4K4: 26 individuals from 21 families reported with Rasopathy-like phenotype, comprising ID/DD, dysmorphic features and congenital anomalies.
Rasopathy v0.99 MAP4K4 Zornitza Stark Marked gene: MAP4K4 as ready
Rasopathy v0.99 MAP4K4 Zornitza Stark Gene: map4k4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5230 MAP4K4 Zornitza Stark edited their review of gene: MAP4K4: Changed rating: GREEN; Changed publications: 37126546; Changed phenotypes: RASopathy, MONDO:0021060, MAP4K4-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.895 SLC26A1 Ain Roesley reviewed gene: SLC26A1: Rating: RED; Mode of pathogenicity: None; Publications: 36719378; Phenotypes: perichondritis, hyposulphatemia, renal sulphate wasting; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Rasopathy v0.99 MAP4K4 Zornitza Stark Classified gene: MAP4K4 as Green List (high evidence)
Rasopathy v0.99 MAP4K4 Zornitza Stark Gene: map4k4 has been classified as Green List (High Evidence).
Rasopathy v0.98 MAP4K4 Zornitza Stark gene: MAP4K4 was added
gene: MAP4K4 was added to Rasopathy. Sources: Literature
Mode of inheritance for gene: MAP4K4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP4K4 were set to 37126546
Phenotypes for gene: MAP4K4 were set to RASopathy, MONDO:0021060, MAP4K4-related
Review for gene: MAP4K4 was set to GREEN
Added comment: 26 individuals from 21 families reported with Rasopathy-like phenotype, comprising ID/DD, dysmorphic features and congenital anomalies.
Sources: Literature
Microcephaly v1.205 MCM6 Suliman Khan changed review comment from: Sources: Literature; to: PMID: 37198333 reported 5 unrelated families with de novo variants in MCM6 gene. Two patients with the same missense variant p.(Cys158Tyr) in zinc finger domain presented with intra-uterine growth retardation, short stature, congenital microcephaly, endocrine features, developmental delay and urogenital anomalies.

In other three unrelated individuals different de novo missense variants were identified in the oligo nucleotide binding (OB)-fold domain. These patients had variable neurodevelopmental features including autism spectrum disorder, developmental delay, and epilepsy.

The clinical features and functional defects related to the zinc binding residue resembled those observed in syndromes related to other MCM components and DNA replication factors (Meier–Gorlin syndrome and Seckel syndrome), while de novo OB-fold domain missense variants were associated with more variable neurodevelopmental phenotypes (PMID: 37198333).
Sources: Literature
Microcephaly v1.205 MCM6 Suliman Khan gene: MCM6 was added
gene: MCM6 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: MCM6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MCM6 were set to PMID: 37198333
Phenotypes for gene: MCM6 were set to Neurodevelopmental disorder, MONDO:0700092, MCM6-related
Review for gene: MCM6 was set to AMBER
Added comment: Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5230 MCM6 Suliman Khan gene: MCM6 was added
gene: MCM6 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MCM6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MCM6 were set to PMID: 37198333
Phenotypes for gene: MCM6 were set to Neurodevelopmental disorder, MONDO:0700092, MCM6-related
Review for gene: MCM6 was set to GREEN
Added comment: PMID: 37198333 reported 5 unrelated families with de novo variants in MCM6 gene. Two patients with the same missense variant p.(Cys158Tyr) in zinc finger domain presented with intra-uterine growth retardation, short stature, congenital microcephaly, endocrine features, developmental delay and urogenital anomalies.

In other three unrelated individuals different de novo missense variants were identified in the oligo nucleotide binding (OB)-fold domain. These patients had variable neurodevelopmental features including autism spectrum disorder, developmental delay, and epilepsy.

The clinical features and functional defects related to the zinc binding residue resembled those observed in syndromes related to other MCM components and DNA replication factors (Meier–Gorlin syndrome and Seckel syndrome), while de novo OB-fold domain missense variants were associated with more variable neurodevelopmental phenotypes (PMID: 37198333).
Sources: Literature
Genomic newborn screening: BabyScreen+ v0.2169 TUBB4B Zornitza Stark Marked gene: TUBB4B as ready
Genomic newborn screening: BabyScreen+ v0.2169 TUBB4B Zornitza Stark Gene: tubb4b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2169 TUBB4B Zornitza Stark Classified gene: TUBB4B as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2169 TUBB4B Zornitza Stark Gene: tubb4b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2168 SUFU Zornitza Stark Marked gene: SUFU as ready
Genomic newborn screening: BabyScreen+ v0.2168 SUFU Zornitza Stark Gene: sufu has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2168 SUFU Zornitza Stark Classified gene: SUFU as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2168 SUFU Zornitza Stark Gene: sufu has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2167 SLITRK6 Zornitza Stark Marked gene: SLITRK6 as ready
Genomic newborn screening: BabyScreen+ v0.2167 SLITRK6 Zornitza Stark Gene: slitrk6 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2167 SLITRK6 Zornitza Stark Tag deafness tag was added to gene: SLITRK6.
Genomic newborn screening: BabyScreen+ v0.2167 SLITRK6 Zornitza Stark Classified gene: SLITRK6 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2167 SLITRK6 Zornitza Stark Gene: slitrk6 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2166 PAX5 Zornitza Stark Marked gene: PAX5 as ready
Genomic newborn screening: BabyScreen+ v0.2166 PAX5 Zornitza Stark Gene: pax5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2166 PAX5 Zornitza Stark Classified gene: PAX5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2166 PAX5 Zornitza Stark Gene: pax5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2165 GREB1L Zornitza Stark Tag deafness tag was added to gene: GREB1L.
Genomic newborn screening: BabyScreen+ v0.2165 MPZL2 Zornitza Stark Marked gene: MPZL2 as ready
Genomic newborn screening: BabyScreen+ v0.2165 MPZL2 Zornitza Stark Gene: mpzl2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2165 MPZL2 Zornitza Stark Classified gene: MPZL2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2165 MPZL2 Zornitza Stark Gene: mpzl2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2164 LMX1A Zornitza Stark Marked gene: LMX1A as ready
Genomic newborn screening: BabyScreen+ v0.2164 LMX1A Zornitza Stark Gene: lmx1a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2164 LMX1A Zornitza Stark Classified gene: LMX1A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2164 LMX1A Zornitza Stark Gene: lmx1a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2163 GREB1L Zornitza Stark Marked gene: GREB1L as ready
Genomic newborn screening: BabyScreen+ v0.2163 GREB1L Zornitza Stark Gene: greb1l has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2163 GREB1L Zornitza Stark Classified gene: GREB1L as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2163 GREB1L Zornitza Stark Gene: greb1l has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2162 NLRP3 Zornitza Stark Marked gene: NLRP3 as ready
Genomic newborn screening: BabyScreen+ v0.2162 NLRP3 Zornitza Stark Gene: nlrp3 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2162 NLRP3 Zornitza Stark Classified gene: NLRP3 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2162 NLRP3 Zornitza Stark Gene: nlrp3 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2161 NLRP3 Zornitza Stark Tag treatable tag was added to gene: NLRP3.
Tag immunological tag was added to gene: NLRP3.
Genomic newborn screening: BabyScreen+ v0.2161 NLRP3 Zornitza Stark gene: NLRP3 was added
gene: NLRP3 was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: NLRP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NLRP3 were set to 25038238
Phenotypes for gene: NLRP3 were set to Familial cold inflammatory syndrome 1, MIM#120100 Muckle-Wells syndrome, MIM#191900 CINCA syndrome, MIM#607115 Deafness, autosomal dominant 34, with or without inflammation, MIM#617772 Keratoendothelitis fugax hereditaria, MIM#148200
Review for gene: NLRP3 was set to AMBER
Added comment: Established gene-disease associations.

Variants in this gene cause a spectrum of clinical phenotypes, ranging from onset in infancy to adult-onset, with variable severity. Genotype-phenotype correlation is unclear, hence not suitable for inclusion at this time.

Treatment: corticosteroids, anakinra, rilonacept and canakinumab.

Non-genetic confirmatory testing: no.
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.2160 AMT Zornitza Stark Tag treatable tag was added to gene: AMT.
Tag metabolic tag was added to gene: AMT.
Genomic newborn screening: BabyScreen+ v0.2160 AMT Zornitza Stark Publications for gene: AMT were set to
Genomic newborn screening: BabyScreen+ v0.2159 AMT Zornitza Stark Classified gene: AMT as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2159 AMT Zornitza Stark Gene: amt has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2158 AMT Zornitza Stark edited their review of gene: AMT: Added comment: Severe infantile forms: treatment does not currently alter outcomes.

Attenuated forms can have onset in childhood, therapy with sodium benzoate and NMDA (The N-methyl-D-aspartate receptor) receptor site antagonists (dextromethorphan, ketamine) but uncertainty about effectiveness.; Changed rating: AMBER; Changed publications: 35683414
Genomic newborn screening: BabyScreen+ v0.2158 GLDC Zornitza Stark Publications for gene: GLDC were set to 16404748; 34513771
Genomic newborn screening: BabyScreen+ v0.2157 GLDC Zornitza Stark Classified gene: GLDC as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2157 GLDC Zornitza Stark Gene: gldc has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2156 GLDC Zornitza Stark changed review comment from: Severe form likely to present clinically, so milder forms, which are more amenable to treatment are likely to be identified through screening.; to: Severe form likely to present clinically, so milder forms, which are more amenable to treatment are likely to be identified through screening.

However, the effectiveness of treatment is not established, PMID 35683414 for a recent review.
Genomic newborn screening: BabyScreen+ v0.2156 GLDC Zornitza Stark edited their review of gene: GLDC: Changed rating: AMBER; Changed publications: 35683414
Genomic newborn screening: BabyScreen+ v0.2156 GLDC Zornitza Stark Classified gene: GLDC as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2156 GLDC Zornitza Stark Gene: gldc has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2155 GLDC Zornitza Stark commented on gene: GLDC: Severe form likely to present clinically, so milder forms, which are more amenable to treatment are likely to be identified through screening.
Genomic newborn screening: BabyScreen+ v0.2155 SAMHD1 Zornitza Stark Classified gene: SAMHD1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2155 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2154 SAMHD1 Zornitza Stark reviewed gene: SAMHD1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 5, MIM# 612952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.2154 CYP27A1 Zornitza Stark Tag for review was removed from gene: CYP27A1.
Tag metabolic tag was added to gene: CYP27A1.
Genomic newborn screening: BabyScreen+ v0.2154 CYP27A1 Zornitza Stark Classified gene: CYP27A1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2154 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2153 CYP27A1 Zornitza Stark edited their review of gene: CYP27A1: Added comment: Average age of onset is in late childhood, but a proportion would have onset < 5yo and early treatment beneficial.; Changed rating: GREEN; Changed publications: 24442603
Calcium and Phosphate disorders v1.0 Bryony Thompson promoted panel to version 1.0
Calcium and Phosphate disorders v0.125 VDR Bryony Thompson Marked gene: VDR as ready
Calcium and Phosphate disorders v0.125 VDR Bryony Thompson Gene: vdr has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v0.125 VDR Bryony Thompson Phenotypes for gene: VDR were changed from to Rickets, vitamin D-resistant, type IIA, MIM# 277440
Genomic newborn screening: BabyScreen+ v0.2153 SGSH Zornitza Stark Publications for gene: SGSH were set to
Genomic newborn screening: BabyScreen+ v0.2152 SGSH Zornitza Stark Classified gene: SGSH as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2152 SGSH Zornitza Stark Gene: sgsh has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2152 SGSH Zornitza Stark Classified gene: SGSH as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2152 SGSH Zornitza Stark Gene: sgsh has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2152 SGSH Zornitza Stark Classified gene: SGSH as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2152 SGSH Zornitza Stark Gene: sgsh has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2151 SGSH Zornitza Stark Tag clinical trial tag was added to gene: SGSH.
Genomic newborn screening: BabyScreen+ v0.2151 SGSH Zornitza Stark reviewed gene: SGSH: Rating: AMBER; Mode of pathogenicity: None; Publications: 31044143; Phenotypes: Mucopolysaccharidosis type IIIA (Sanfilippo A), MIM# 252900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Calcium and Phosphate disorders v0.124 VDR Bryony Thompson Publications for gene: VDR were set to
Calcium and Phosphate disorders v0.123 VDR Bryony Thompson Mode of inheritance for gene: VDR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Calcium and Phosphate disorders v0.122 SLC34A1 Bryony Thompson Marked gene: SLC34A1 as ready
Calcium and Phosphate disorders v0.122 SLC34A1 Bryony Thompson Gene: slc34a1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v0.122 SLC34A1 Bryony Thompson Phenotypes for gene: SLC34A1 were changed from to Hypercalcaemia, infantile, 2 MIM#616963
Calcium and Phosphate disorders v0.121 SLC34A1 Bryony Thompson Publications for gene: SLC34A1 were set to
Calcium and Phosphate disorders v0.120 SLC34A1 Bryony Thompson Mode of inheritance for gene: SLC34A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Calcium and Phosphate disorders v0.119 PTH1R Bryony Thompson Marked gene: PTH1R as ready
Calcium and Phosphate disorders v0.119 PTH1R Bryony Thompson Gene: pth1r has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v0.119 PTH1R Bryony Thompson Phenotypes for gene: PTH1R were changed from to Metaphyseal chondrodysplasia, Murk Jansen type, MIM# 156400; MONDO:0007982
Calcium and Phosphate disorders v0.118 PTH1R Bryony Thompson Publications for gene: PTH1R were set to
Calcium and Phosphate disorders v0.117 PTH1R Bryony Thompson Mode of pathogenicity for gene: PTH1R was changed from to Other
Calcium and Phosphate disorders v0.116 PTH1R Bryony Thompson Mode of inheritance for gene: PTH1R was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Calcium and Phosphate disorders v0.115 GNA11 Bryony Thompson Marked gene: GNA11 as ready
Calcium and Phosphate disorders v0.115 GNA11 Bryony Thompson Gene: gna11 has been classified as Green List (High Evidence).
Mendeliome v1.895 MCM6 Suliman Khan reviewed gene: MCM6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37198333; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, MCM6-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Calcium and Phosphate disorders v0.115 GNA11 Bryony Thompson Phenotypes for gene: GNA11 were changed from to Hypocalcemia, autosomal dominant 2 MIM#615361; Hypocalciuric hypercalcemia, type II MIM#145981
Calcium and Phosphate disorders v0.114 GNA11 Bryony Thompson Publications for gene: GNA11 were set to
Calcium and Phosphate disorders v0.113 GNA11 Bryony Thompson Mode of pathogenicity for gene: GNA11 was changed from to Other
Calcium and Phosphate disorders v0.112 GNA11 Bryony Thompson Mode of inheritance for gene: GNA11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Calcium and Phosphate disorders v0.111 GALNT3 Bryony Thompson Marked gene: GALNT3 as ready
Calcium and Phosphate disorders v0.111 GALNT3 Bryony Thompson Gene: galnt3 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v0.111 GALNT3 Bryony Thompson Phenotypes for gene: GALNT3 were changed from to Tumoral calcinosis, hyperphosphatemic, familial, 1, MIM# 211900
Calcium and Phosphate disorders v0.110 GALNT3 Bryony Thompson Publications for gene: GALNT3 were set to
Calcium and Phosphate disorders v0.109 GALNT3 Bryony Thompson Mode of inheritance for gene: GALNT3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Calcium and Phosphate disorders v0.108 FGF23 Bryony Thompson Marked gene: FGF23 as ready
Calcium and Phosphate disorders v0.108 FGF23 Bryony Thompson Gene: fgf23 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v0.108 FGF23 Bryony Thompson Phenotypes for gene: FGF23 were changed from to autosomal dominant hypophosphatemic rickets MONDO:0008660; familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome MONDO:0100251
Calcium and Phosphate disorders v0.107 FGF23 Bryony Thompson Publications for gene: FGF23 were set to
Calcium and Phosphate disorders v0.106 FGF23 Bryony Thompson Mode of pathogenicity for gene: FGF23 was changed from to Other
Calcium and Phosphate disorders v0.105 FGF23 Bryony Thompson Mode of inheritance for gene: FGF23 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Calcium and Phosphate disorders v0.104 FAM111A Bryony Thompson Marked gene: FAM111A as ready
Calcium and Phosphate disorders v0.104 FAM111A Bryony Thompson Gene: fam111a has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v0.104 FAM111A Bryony Thompson Phenotypes for gene: FAM111A were changed from to autosomal dominant Kenny-Caffey syndrome MONDO:0007478
Calcium and Phosphate disorders v0.103 FAM111A Bryony Thompson Publications for gene: FAM111A were set to
Calcium and Phosphate disorders v0.102 FAM111A Bryony Thompson Mode of inheritance for gene: FAM111A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Calcium and Phosphate disorders v0.101 ENPP1 Bryony Thompson Marked gene: ENPP1 as ready
Calcium and Phosphate disorders v0.101 ENPP1 Bryony Thompson Gene: enpp1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v0.101 ENPP1 Bryony Thompson Phenotypes for gene: ENPP1 were changed from to Hypophosphatemic rickets, autosomal recessive, 2, MIM# 613312
Calcium and Phosphate disorders v0.100 ENPP1 Bryony Thompson Publications for gene: ENPP1 were set to
Calcium and Phosphate disorders v0.99 ENPP1 Bryony Thompson Mode of inheritance for gene: ENPP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Calcium and Phosphate disorders v0.98 DMP1 Bryony Thompson Marked gene: DMP1 as ready
Calcium and Phosphate disorders v0.98 DMP1 Bryony Thompson Gene: dmp1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v0.98 DMP1 Bryony Thompson Phenotypes for gene: DMP1 were changed from to Hypophosphatemic rickets MIM#241520
Calcium and Phosphate disorders v0.97 DMP1 Bryony Thompson Publications for gene: DMP1 were set to
Calcium and Phosphate disorders v0.96 DMP1 Bryony Thompson Mode of inheritance for gene: DMP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Calcium and Phosphate disorders v0.95 TRPV6 Bryony Thompson Marked gene: TRPV6 as ready
Calcium and Phosphate disorders v0.95 TRPV6 Bryony Thompson Gene: trpv6 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v0.95 TRPV6 Bryony Thompson Classified gene: TRPV6 as Green List (high evidence)
Calcium and Phosphate disorders v0.95 TRPV6 Bryony Thompson Gene: trpv6 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v0.94 CYP2R1 Bryony Thompson Marked gene: CYP2R1 as ready
Calcium and Phosphate disorders v0.94 CYP2R1 Bryony Thompson Gene: cyp2r1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v0.94 CYP2R1 Bryony Thompson Phenotypes for gene: CYP2R1 were changed from to Rickets due to defect in vitamin D 25-hydroxylation deficiency MIM#600081
Calcium and Phosphate disorders v0.93 CYP2R1 Bryony Thompson Publications for gene: CYP2R1 were set to
Calcium and Phosphate disorders v0.92 CYP2R1 Bryony Thompson Mode of inheritance for gene: CYP2R1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Calcium and Phosphate disorders v0.91 CYP27B1 Bryony Thompson Marked gene: CYP27B1 as ready
Calcium and Phosphate disorders v0.91 CYP27B1 Bryony Thompson Gene: cyp27b1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v0.91 CYP27B1 Bryony Thompson Phenotypes for gene: CYP27B1 were changed from to Vitamin D-dependent rickets, type I MIM#264700
Calcium and Phosphate disorders v0.90 CYP27B1 Bryony Thompson Publications for gene: CYP27B1 were set to
Calcium and Phosphate disorders v0.89 CYP27B1 Bryony Thompson Mode of inheritance for gene: CYP27B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Calcium and Phosphate disorders v0.88 CDC73 Bryony Thompson Marked gene: CDC73 as ready
Calcium and Phosphate disorders v0.88 CDC73 Bryony Thompson Gene: cdc73 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v0.88 CDC73 Bryony Thompson Phenotypes for gene: CDC73 were changed from to Hyperparathyroidism-jaw tumour syndrome, MIM# 145001; Hyperparathyroidism, familial primary, MIM# 145000
Calcium and Phosphate disorders v0.87 CDC73 Bryony Thompson Publications for gene: CDC73 were set to
Calcium and Phosphate disorders v0.86 CDC73 Bryony Thompson Mode of inheritance for gene: CDC73 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Calcium and Phosphate disorders v0.85 CASR Bryony Thompson Marked gene: CASR as ready
Calcium and Phosphate disorders v0.85 CASR Bryony Thompson Gene: casr has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v0.85 CASR Bryony Thompson Phenotypes for gene: CASR were changed from to Hyperparathyroidism, neonatal MIM#239200; Hypocalcemia, autosomal dominant MIM#601198; Hypocalcemia autosomal dominant, with Bartter syndrome MIM#601198; hypercalcemia, type I MIM#145980
Calcium and Phosphate disorders v0.84 CASR Bryony Thompson Publications for gene: CASR were set to
Calcium and Phosphate disorders v0.83 CASR Bryony Thompson Mode of inheritance for gene: CASR was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Calcium and Phosphate disorders v0.81 TRPV6 Bryony Thompson gene: TRPV6 was added
gene: TRPV6 was added to Calcium and Phosphate disorders. Sources: Other
Mode of inheritance for gene: TRPV6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPV6 were set to 31930989; 29861107
Phenotypes for gene: TRPV6 were set to Hyperparathyroidism, transient neonatal, MIM# 618188
Motor Neurone Disease v0.165 ANG Zornitza Stark Marked gene: ANG as ready
Motor Neurone Disease v0.165 ANG Zornitza Stark Gene: ang has been classified as Green List (High Evidence).
Motor Neurone Disease v0.165 ANG Zornitza Stark Phenotypes for gene: ANG were changed from to Amyotrophic Lateral Sclerosis 9 (MONDO: 0012753; MIM#611895)
Motor Neurone Disease v0.164 ANG Zornitza Stark Publications for gene: ANG were set to
Motor Neurone Disease v0.163 ANG Zornitza Stark Mode of inheritance for gene: ANG was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.162 ALS2 Zornitza Stark Marked gene: ALS2 as ready
Motor Neurone Disease v0.162 ALS2 Zornitza Stark Gene: als2 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.162 ALS2 Zornitza Stark Phenotypes for gene: ALS2 were changed from to Amyotrophic lateral sclerosis 2, juvenile (MIM# 205100; MONDO: MONDO:0008780)
Motor Neurone Disease v0.161 ALS2 Zornitza Stark Publications for gene: ALS2 were set to
Motor Neurone Disease v0.160 ALS2 Zornitza Stark Mode of inheritance for gene: ALS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.159 ASCC1 Zornitza Stark Marked gene: ASCC1 as ready
Motor Neurone Disease v0.159 ASCC1 Zornitza Stark Gene: ascc1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.159 ASCC1 Zornitza Stark Phenotypes for gene: ASCC1 were changed from to spinal muscular atrophy with congenital bone fractures 2 (MONDO:0014807; MIM#616867)
Motor Neurone Disease v0.158 ASCC1 Zornitza Stark Publications for gene: ASCC1 were set to
Motor Neurone Disease v0.157 ASCC1 Zornitza Stark Mode of inheritance for gene: ASCC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.166 APTX Zornitza Stark Marked gene: APTX as ready
Hereditary Neuropathy - complex v0.166 APTX Zornitza Stark Gene: aptx has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.166 APTX Zornitza Stark Phenotypes for gene: APTX were changed from Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia; Hereditary Neuropathies to Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia (MIM#208920)
Hereditary Neuropathy - complex v0.165 APTX Zornitza Stark Publications for gene: APTX were set to
Hereditary Neuropathy - complex v0.164 B4GALNT1 Zornitza Stark Marked gene: B4GALNT1 as ready
Hereditary Neuropathy - complex v0.164 B4GALNT1 Zornitza Stark Gene: b4galnt1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.164 B4GALNT1 Zornitza Stark Phenotypes for gene: B4GALNT1 were changed from Spastic paraplegia, intellectual disability, ataxia, dystonia, axonal sensory-motor neuropathy to Spastic paraplegia 26, autosomal recessive (MIM#609195; MONDO:0012213)
Hereditary Neuropathy - complex v0.163 B4GALNT1 Zornitza Stark Publications for gene: B4GALNT1 were set to
Hereditary Neuropathy - complex v0.162 B4GALNT1 Zornitza Stark Classified gene: B4GALNT1 as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.162 B4GALNT1 Zornitza Stark Gene: b4galnt1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.161 BAG3 Zornitza Stark Marked gene: BAG3 as ready
Hereditary Neuropathy - complex v0.161 BAG3 Zornitza Stark Gene: bag3 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.161 BAG3 Zornitza Stark Phenotypes for gene: BAG3 were changed from Myopathy, myofibrillar, 6 612954; Cardiomyopathy, dilated, 1HH, 613881; HMSN to Myopathy, myofibrillar, 6 (MIM#612954; MONDO:0013061)
Hereditary Neuropathy - complex v0.160 BAG3 Zornitza Stark Publications for gene: BAG3 were set to
Hereditary Neuropathy - complex v0.159 BAG3 Zornitza Stark Classified gene: BAG3 as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.159 BAG3 Zornitza Stark Gene: bag3 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.158 CNTNAP1 Zornitza Stark Marked gene: CNTNAP1 as ready
Hereditary Neuropathy - complex v0.158 CNTNAP1 Zornitza Stark Gene: cntnap1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.158 CNTNAP1 Zornitza Stark Phenotypes for gene: CNTNAP1 were changed from Hypomyelinating neuropathy, congenital, 3, 618186 to Hypomyelinating neuropathy, congenital, 3 (MONDO:0017049; MIM#618186)
Hereditary Neuropathy - complex v0.157 CNTNAP1 Zornitza Stark Publications for gene: CNTNAP1 were set to
Hereditary Neuropathy - complex v0.156 COX10 Zornitza Stark Marked gene: COX10 as ready
Hereditary Neuropathy - complex v0.156 COX10 Zornitza Stark Gene: cox10 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.156 COX10 Zornitza Stark Phenotypes for gene: COX10 were changed from Hepatic failure, early-onset, and neurologic disorder due to cytochrome C oxidase deficiency; HMSN to Mitochondrial complex IV deficiency, nuclear type 3 (MIM#619046)
Hereditary Neuropathy - complex v0.155 COX10 Zornitza Stark Publications for gene: COX10 were set to
Hereditary Neuropathy - complex v0.154 COX10 Zornitza Stark Classified gene: COX10 as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.154 COX10 Zornitza Stark Gene: cox10 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.153 CTDP1 Zornitza Stark Marked gene: CTDP1 as ready
Hereditary Neuropathy - complex v0.153 CTDP1 Zornitza Stark Gene: ctdp1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.153 CTDP1 Zornitza Stark Phenotypes for gene: CTDP1 were changed from Congenital cataract, facial dysmorphism and demyelinating neuropathy (CCFDN); HMSN to Congenital cataracts, facial dysmorphism, and neuropathy (MIM#604168)
Hereditary Neuropathy - complex v0.152 CTDP1 Zornitza Stark Publications for gene: CTDP1 were set to
Hereditary Neuropathy - complex v0.151 CTDP1 Zornitza Stark Tag deep intronic tag was added to gene: CTDP1.
Tag founder tag was added to gene: CTDP1.
Hereditary Neuropathy - complex v0.151 CTDP1 Zornitza Stark reviewed gene: CTDP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital cataracts, facial dysmorphism, and neuropathy (MIM#604168); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.151 CYP2U1 Zornitza Stark Marked gene: CYP2U1 as ready
Hereditary Neuropathy - complex v0.151 CYP2U1 Zornitza Stark Gene: cyp2u1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.151 CYP2U1 Zornitza Stark Phenotypes for gene: CYP2U1 were changed from Onset first decade, spastic paraplegia, rarely dystonia and cognitive impairment, subclinical sensory-motor axonal neuropathy to Spastic paraplegia 56, autosomal recessive, MIM#615030
Hereditary Neuropathy - complex v0.150 CYP2U1 Zornitza Stark Publications for gene: CYP2U1 were set to
Fetal anomalies v1.109 RASA1 Zornitza Stark Publications for gene: RASA1 were set to 33461977
Fetal anomalies v1.108 RASA1 Zornitza Stark edited their review of gene: RASA1: Added comment: PMID 36980822: 21 cases presenting with hydrops.; Changed publications: 33461977, 36980822
Hydrops fetalis v0.300 RASA1 Zornitza Stark Publications for gene: RASA1 were set to 26096958
Hydrops fetalis v0.299 RASA1 Zornitza Stark Classified gene: RASA1 as Green List (high evidence)
Hydrops fetalis v0.299 RASA1 Zornitza Stark Gene: rasa1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.86 ADCY5 Zornitza Stark Marked gene: ADCY5 as ready
Cerebral Palsy v1.86 ADCY5 Zornitza Stark Gene: adcy5 has been classified as Green List (High Evidence).
Cerebral Palsy v1.86 ADCY5 Zornitza Stark Classified gene: ADCY5 as Green List (high evidence)
Cerebral Palsy v1.86 ADCY5 Zornitza Stark Gene: adcy5 has been classified as Green List (High Evidence).
Cerebral Palsy v1.85 ACTB Zornitza Stark Marked gene: ACTB as ready
Cerebral Palsy v1.85 ACTB Zornitza Stark Gene: actb has been classified as Green List (High Evidence).
Cerebral Palsy v1.85 ACTB Zornitza Stark Mode of inheritance for gene: ACTB was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.84 ACTB Zornitza Stark Classified gene: ACTB as Green List (high evidence)
Cerebral Palsy v1.84 ACTB Zornitza Stark Gene: actb has been classified as Green List (High Evidence).
Cerebral Palsy v1.83 ACADM Zornitza Stark Marked gene: ACADM as ready
Cerebral Palsy v1.83 ACADM Zornitza Stark Gene: acadm has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.83 ACADM Zornitza Stark Classified gene: ACADM as Amber List (moderate evidence)
Cerebral Palsy v1.83 ACADM Zornitza Stark Gene: acadm has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.82 ADNP Zornitza Stark Marked gene: ADNP as ready
Cerebral Palsy v1.82 ADNP Zornitza Stark Gene: adnp has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.82 ADNP Zornitza Stark Classified gene: ADNP as Amber List (moderate evidence)
Cerebral Palsy v1.82 ADNP Zornitza Stark Gene: adnp has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.81 AHDC1 Zornitza Stark Marked gene: AHDC1 as ready
Cerebral Palsy v1.81 AHDC1 Zornitza Stark Gene: ahdc1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.81 AHDC1 Zornitza Stark Classified gene: AHDC1 as Green List (high evidence)
Cerebral Palsy v1.81 AHDC1 Zornitza Stark Gene: ahdc1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.80 AKT3 Zornitza Stark Marked gene: AKT3 as ready
Cerebral Palsy v1.80 AKT3 Zornitza Stark Gene: akt3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.80 AKT3 Zornitza Stark Phenotypes for gene: AKT3 were changed from to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, MIM# 615937
Cerebral Palsy v1.79 AKT3 Zornitza Stark Classified gene: AKT3 as Red List (low evidence)
Cerebral Palsy v1.79 AKT3 Zornitza Stark Gene: akt3 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.78 AKT3 Zornitza Stark reviewed gene: AKT3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, MIM# 615937; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.78 ARG1 Zornitza Stark Marked gene: ARG1 as ready
Cerebral Palsy v1.78 ARG1 Zornitza Stark Gene: arg1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.78 ARG1 Zornitza Stark Classified gene: ARG1 as Green List (high evidence)
Cerebral Palsy v1.78 ARG1 Zornitza Stark Gene: arg1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.77 ARID2 Zornitza Stark Marked gene: ARID2 as ready
Cerebral Palsy v1.77 ARID2 Zornitza Stark Gene: arid2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.77 ARID2 Zornitza Stark Classified gene: ARID2 as Green List (high evidence)
Cerebral Palsy v1.77 ARID2 Zornitza Stark Gene: arid2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.76 ATP7A Zornitza Stark Marked gene: ATP7A as ready
Cerebral Palsy v1.76 ATP7A Zornitza Stark Gene: atp7a has been classified as Green List (High Evidence).
Cerebral Palsy v1.76 ATP7A Zornitza Stark Classified gene: ATP7A as Green List (high evidence)
Cerebral Palsy v1.76 ATP7A Zornitza Stark Gene: atp7a has been classified as Green List (High Evidence).
Cerebral Palsy v1.75 ATP8A2 Zornitza Stark Marked gene: ATP8A2 as ready
Cerebral Palsy v1.75 ATP8A2 Zornitza Stark Gene: atp8a2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.75 ATP8A2 Zornitza Stark Classified gene: ATP8A2 as Green List (high evidence)
Cerebral Palsy v1.75 ATP8A2 Zornitza Stark Gene: atp8a2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.74 BCL11A Zornitza Stark Publications for gene: BCL11A were set to
Cerebral Palsy v1.73 BCL11A Zornitza Stark Classified gene: BCL11A as Green List (high evidence)
Cerebral Palsy v1.73 BCL11A Zornitza Stark Gene: bcl11a has been classified as Green List (High Evidence).
Cerebral Palsy v1.72 BRAT1 Zornitza Stark Marked gene: BRAT1 as ready
Cerebral Palsy v1.72 BRAT1 Zornitza Stark Gene: brat1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.72 BRAT1 Zornitza Stark Classified gene: BRAT1 as Amber List (moderate evidence)
Cerebral Palsy v1.72 BRAT1 Zornitza Stark Gene: brat1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.71 CACNA1A Zornitza Stark Phenotypes for gene: CACNA1A were changed from Developemental and epileptic encephalopathy 42, MIM# 617106; Episodic ataxia, type 2, MIM# 108500; Migraine, familial hemiplegic, 1, MIM# 141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia 141500; Spinocerebellar ataxia 6, MIM# 183086 to Developemental and epileptic encephalopathy 42, MIM# 617106; Episodic ataxia, type 2, MIM# 108500; Spinocerebellar ataxia 6, MIM# 183086
Cerebral Palsy v1.70 CACNA1A Zornitza Stark Publications for gene: CACNA1A were set to 29761117
Cerebral Palsy v1.69 CACNA1A Zornitza Stark Classified gene: CACNA1A as Green List (high evidence)
Cerebral Palsy v1.69 CACNA1A Zornitza Stark Gene: cacna1a has been classified as Green List (High Evidence).
Cerebral Palsy v1.68 CASK Zornitza Stark Marked gene: CASK as ready
Cerebral Palsy v1.68 CASK Zornitza Stark Gene: cask has been classified as Green List (High Evidence).
Cerebral Palsy v1.68 CASK Zornitza Stark Classified gene: CASK as Green List (high evidence)
Cerebral Palsy v1.68 CASK Zornitza Stark Gene: cask has been classified as Green List (High Evidence).
Cerebral Palsy v1.67 CDKL5 Zornitza Stark Marked gene: CDKL5 as ready
Cerebral Palsy v1.67 CDKL5 Zornitza Stark Gene: cdkl5 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.67 CDKL5 Zornitza Stark Phenotypes for gene: CDKL5 were changed from to Developmental and epileptic encephalopathy 2, MIM# 300672
Cerebral Palsy v1.66 CDKL5 Zornitza Stark Classified gene: CDKL5 as Amber List (moderate evidence)
Cerebral Palsy v1.66 CDKL5 Zornitza Stark Gene: cdkl5 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.65 CHD8 Zornitza Stark Marked gene: CHD8 as ready
Cerebral Palsy v1.65 CHD8 Zornitza Stark Gene: chd8 has been classified as Green List (High Evidence).
Cerebral Palsy v1.65 CHD8 Zornitza Stark Classified gene: CHD8 as Green List (high evidence)
Cerebral Palsy v1.65 CHD8 Zornitza Stark Gene: chd8 has been classified as Green List (High Evidence).
Cerebral Palsy v1.64 ATP7B Zornitza Stark Marked gene: ATP7B as ready
Cerebral Palsy v1.64 ATP7B Zornitza Stark Gene: atp7b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.64 ATP7B Zornitza Stark Classified gene: ATP7B as Red List (low evidence)
Cerebral Palsy v1.64 ATP7B Zornitza Stark Gene: atp7b has been classified as Red List (Low Evidence).
Cerebral Palsy v1.63 CLCN4 Zornitza Stark Marked gene: CLCN4 as ready
Cerebral Palsy v1.63 CLCN4 Zornitza Stark Gene: clcn4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.63 CLCN4 Zornitza Stark Classified gene: CLCN4 as Red List (low evidence)
Cerebral Palsy v1.63 CLCN4 Zornitza Stark Gene: clcn4 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.62 CLTC Zornitza Stark Marked gene: CLTC as ready
Cerebral Palsy v1.62 CLTC Zornitza Stark Gene: cltc has been classified as Green List (High Evidence).
Cerebral Palsy v1.62 CLTC Zornitza Stark Classified gene: CLTC as Green List (high evidence)
Cerebral Palsy v1.62 CLTC Zornitza Stark Gene: cltc has been classified as Green List (High Evidence).
Cerebral Palsy v1.61 COL4A1 Zornitza Stark Phenotypes for gene: COL4A1 were changed from {Hemorrhage, intracerebral, susceptibility to}, MIM# 614519 to {Hemorrhage, intracerebral, susceptibility to}, MIM# 614519; Brain small vessel disease MIM#614483
Cerebral Palsy v1.60 COL4A1 Zornitza Stark Publications for gene: COL4A1 were set to 31700678; 17379824
Cerebral Palsy v1.59 COL4A1 Zornitza Stark Classified gene: COL4A1 as Green List (high evidence)
Cerebral Palsy v1.59 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.58 CREBBP Zornitza Stark Marked gene: CREBBP as ready
Cerebral Palsy v1.58 CREBBP Zornitza Stark Gene: crebbp has been classified as Green List (High Evidence).
Cerebral Palsy v1.58 CREBBP Zornitza Stark Classified gene: CREBBP as Green List (high evidence)
Cerebral Palsy v1.58 CREBBP Zornitza Stark Gene: crebbp has been classified as Green List (High Evidence).
Cerebral Palsy v1.57 CTBP1 Zornitza Stark Marked gene: CTBP1 as ready
Cerebral Palsy v1.57 CTBP1 Zornitza Stark Gene: ctbp1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.57 CTBP1 Zornitza Stark Classified gene: CTBP1 as Amber List (moderate evidence)
Cerebral Palsy v1.57 CTBP1 Zornitza Stark Gene: ctbp1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.56 CTNNA2 Zornitza Stark Marked gene: CTNNA2 as ready
Cerebral Palsy v1.56 CTNNA2 Zornitza Stark Gene: ctnna2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.56 CTNNA2 Zornitza Stark Classified gene: CTNNA2 as Green List (high evidence)
Cerebral Palsy v1.56 CTNNA2 Zornitza Stark Gene: ctnna2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.55 DOCK6 Zornitza Stark Marked gene: DOCK6 as ready
Cerebral Palsy v1.55 DOCK6 Zornitza Stark Gene: dock6 has been classified as Green List (High Evidence).
Cerebral Palsy v1.55 DOCK6 Zornitza Stark Classified gene: DOCK6 as Green List (high evidence)
Cerebral Palsy v1.55 DOCK6 Zornitza Stark Gene: dock6 has been classified as Green List (High Evidence).
Cerebral Palsy v1.54 DYNC1H1 Zornitza Stark Marked gene: DYNC1H1 as ready
Cerebral Palsy v1.54 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.54 DYNC1H1 Zornitza Stark Phenotypes for gene: DYNC1H1 were changed from Charcot-Marie-Tooth disease MIM#614228; Cortical dysplasia, complex MIM#614563; Spinal muscular atrophy, lower extremity-predominant MIM#158600 to Cortical dysplasia, complex MIM#614563
Cerebral Palsy v1.53 DYNC1H1 Zornitza Stark Classified gene: DYNC1H1 as Green List (high evidence)
Cerebral Palsy v1.53 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.52 DYRK1A Zornitza Stark Marked gene: DYRK1A as ready
Cerebral Palsy v1.52 DYRK1A Zornitza Stark Gene: dyrk1a has been classified as Green List (High Evidence).
Cerebral Palsy v1.52 DYRK1A Zornitza Stark Classified gene: DYRK1A as Green List (high evidence)
Cerebral Palsy v1.52 DYRK1A Zornitza Stark Gene: dyrk1a has been classified as Green List (High Evidence).
Cerebral Palsy v1.51 EXOSC3 Zornitza Stark Marked gene: EXOSC3 as ready
Cerebral Palsy v1.51 EXOSC3 Zornitza Stark Gene: exosc3 has been classified as Green List (High Evidence).
Cerebral Palsy v1.51 EXOSC3 Zornitza Stark Classified gene: EXOSC3 as Green List (high evidence)
Cerebral Palsy v1.51 EXOSC3 Zornitza Stark Gene: exosc3 has been classified as Green List (High Evidence).
Cerebral Palsy v1.50 FAM126A Zornitza Stark Marked gene: FAM126A as ready
Cerebral Palsy v1.50 FAM126A Zornitza Stark Gene: fam126a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.50 FAM126A Zornitza Stark Classified gene: FAM126A as Red List (low evidence)
Cerebral Palsy v1.50 FAM126A Zornitza Stark Gene: fam126a has been classified as Red List (Low Evidence).
Cerebral Palsy v1.49 ERCC8 Zornitza Stark Marked gene: ERCC8 as ready
Cerebral Palsy v1.49 ERCC8 Zornitza Stark Gene: ercc8 has been classified as Green List (High Evidence).
Cerebral Palsy v1.49 ERCC8 Zornitza Stark Classified gene: ERCC8 as Green List (high evidence)
Cerebral Palsy v1.49 ERCC8 Zornitza Stark Gene: ercc8 has been classified as Green List (High Evidence).
Cerebral Palsy v1.48 ELP2 Zornitza Stark Marked gene: ELP2 as ready
Cerebral Palsy v1.48 ELP2 Zornitza Stark Gene: elp2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.48 ELP2 Zornitza Stark Classified gene: ELP2 as Green List (high evidence)
Cerebral Palsy v1.48 ELP2 Zornitza Stark Gene: elp2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.47 EEF1A2 Zornitza Stark Marked gene: EEF1A2 as ready
Cerebral Palsy v1.47 EEF1A2 Zornitza Stark Gene: eef1a2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.47 EEF1A2 Zornitza Stark Classified gene: EEF1A2 as Amber List (moderate evidence)
Cerebral Palsy v1.47 EEF1A2 Zornitza Stark Gene: eef1a2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.46 FAR1 Zornitza Stark Marked gene: FAR1 as ready
Cerebral Palsy v1.46 FAR1 Zornitza Stark Gene: far1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.46 FAR1 Zornitza Stark Classified gene: FAR1 as Green List (high evidence)
Cerebral Palsy v1.46 FAR1 Zornitza Stark Gene: far1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.45 FARS2 Zornitza Stark Marked gene: FARS2 as ready
Cerebral Palsy v1.45 FARS2 Zornitza Stark Gene: fars2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.45 FARS2 Zornitza Stark Classified gene: FARS2 as Green List (high evidence)
Cerebral Palsy v1.45 FARS2 Zornitza Stark Gene: fars2 has been classified as Green List (High Evidence).
Cerebral Palsy v1.44 ATM Zornitza Stark Marked gene: ATM as ready
Cerebral Palsy v1.44 ATM Zornitza Stark Gene: atm has been classified as Green List (High Evidence).
Cerebral Palsy v1.44 ATM Zornitza Stark Classified gene: ATM as Green List (high evidence)
Cerebral Palsy v1.44 ATM Zornitza Stark Gene: atm has been classified as Green List (High Evidence).
Cerebral Palsy v1.43 FH Zornitza Stark Marked gene: FH as ready
Cerebral Palsy v1.43 FH Zornitza Stark Gene: fh has been classified as Green List (High Evidence).
Cerebral Palsy v1.43 FH Zornitza Stark Classified gene: FH as Green List (high evidence)
Cerebral Palsy v1.43 FH Zornitza Stark Gene: fh has been classified as Green List (High Evidence).
Cerebral Palsy v1.42 FLNA Zornitza Stark Marked gene: FLNA as ready
Cerebral Palsy v1.42 FLNA Zornitza Stark Gene: flna has been classified as Red List (Low Evidence).
Cerebral Palsy v1.42 FLNA Zornitza Stark Phenotypes for gene: FLNA were changed from Cardiac valvular dysplasia MIM#314400; Congenital short bowel syndrome MIM#300048; Frontometaphyseal dysplasia MIM#305620; Heterotopia, periventricular MIM#300049; Intestinal pseudoobstruction MIM#300048; Melnick-Needles syndrome MIM#309350; Otopalatodigital syndrome I MIM#311300; Otopalatodigital syndrome II MIM# 304120; Terminal osseous dysplasia MIM#300244 to Heterotopia, periventricular, 1, MIM#300049
Cerebral Palsy v1.41 FLNA Zornitza Stark Classified gene: FLNA as Red List (low evidence)
Cerebral Palsy v1.41 FLNA Zornitza Stark Gene: flna has been classified as Red List (Low Evidence).
Cerebral Palsy v1.40 FLNA Zornitza Stark reviewed gene: FLNA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Heterotopia, periventricular, 1, MIM#300049; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.40 FRRS1L Zornitza Stark Marked gene: FRRS1L as ready
Cerebral Palsy v1.40 FRRS1L Zornitza Stark Gene: frrs1l has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.40 FRRS1L Zornitza Stark Classified gene: FRRS1L as Amber List (moderate evidence)
Cerebral Palsy v1.40 FRRS1L Zornitza Stark Gene: frrs1l has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.39 FRRS1L Zornitza Stark reviewed gene: FRRS1L: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy MIM#616981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.39 GABRB1 Zornitza Stark Marked gene: GABRB1 as ready
Cerebral Palsy v1.39 GABRB1 Zornitza Stark Gene: gabrb1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.39 GABRB1 Zornitza Stark Classified gene: GABRB1 as Red List (low evidence)
Cerebral Palsy v1.39 GABRB1 Zornitza Stark Gene: gabrb1 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.38 GABRB2 Zornitza Stark Marked gene: GABRB2 as ready
Cerebral Palsy v1.38 GABRB2 Zornitza Stark Gene: gabrb2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.38 GABRB2 Zornitza Stark Classified gene: GABRB2 as Amber List (moderate evidence)
Cerebral Palsy v1.38 GABRB2 Zornitza Stark Gene: gabrb2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.37 GCDH Zornitza Stark Marked gene: GCDH as ready
Cerebral Palsy v1.37 GCDH Zornitza Stark Gene: gcdh has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.37 GCDH Zornitza Stark Classified gene: GCDH as Amber List (moderate evidence)
Cerebral Palsy v1.37 GCDH Zornitza Stark Gene: gcdh has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.36 GCDH Luisa Weiss gene: GCDH was added
gene: GCDH was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GCDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCDH were set to 30542205; 26593172
Phenotypes for gene: GCDH were set to Glutaricaciduria, type I MIM#231670
Review for gene: GCDH was set to AMBER
Added comment: One case in a larger cohort study of patients with atypical CP, no mutation information given. One case report of one boy diagnosed with dystonic CP and homozygous missense mutation in GCDH with biochemically corresponding features.
Sources: Literature
Cerebral Palsy v1.36 GABRB2 Luisa Weiss gene: GABRB2 was added
gene: GABRB2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GABRB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRB2 were set to 33528536
Phenotypes for gene: GABRB2 were set to Developmental and epileptic encephalopathy MIM#617829
Review for gene: GABRB2 was set to AMBER
Added comment: Two cases in a large CP cohort study with heterozygous de novo mutations in GABRB2.
Sources: Literature
Cerebral Palsy v1.36 GABRB1 Luisa Weiss gene: GABRB1 was added
gene: GABRB1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GABRB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRB1 were set to 34540776
Phenotypes for gene: GABRB1 were set to Developmental and epileptic encephalopathy MIM#617153
Review for gene: GABRB1 was set to RED
Added comment: One large cohort study on CP patients from Iran presents one patient with a heterozygous mutation in GABRB1 and atypical CP with developmental delay, ID and microcephaly. The patient's mutation (NM_000812:c.1243G>C,p.G415R) is present in a heterozygous state in the patient and no information about inheritance is given. The authors propose a recessively inherited disease. The variant is classified as a variant of unknown significance in this paper.
Sources: Literature
Cerebral Palsy v1.36 FRRS1L Luisa Weiss gene: FRRS1L was added
gene: FRRS1L was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FRRS1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRRS1L were set to 33528536; 27236917
Phenotypes for gene: FRRS1L were set to Developmental and epileptic encephalopathy MIM#616981
Review for gene: FRRS1L was set to GREEN
Added comment: Three independent patients in a large CP cohort study with the same recurrent homozygous mutation (NM_014334:c.735_737del,p.245_246del).
Another cohort study of multiple patients with biallelic FRRS1L mutations and epileptic-dyskinetic encephalopathy described on patient (individual 4_II-1) with non-progressive movement disorder in addition to epilepsy.
Sources: Literature
Cerebral Palsy v1.36 FLNA Luisa Weiss gene: FLNA was added
gene: FLNA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FLNA was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: FLNA were set to 29706646; 34077496; 25817843
Phenotypes for gene: FLNA were set to Cardiac valvular dysplasia MIM#314400; Congenital short bowel syndrome MIM#300048; Frontometaphyseal dysplasia MIM#305620; Heterotopia, periventricular MIM#300049; Intestinal pseudoobstruction MIM#300048; Melnick-Needles syndrome MIM#309350; Otopalatodigital syndrome I MIM#311300; Otopalatodigital syndrome II MIM# 304120; Terminal osseous dysplasia MIM#300244
Review for gene: FLNA was set to GREEN
Added comment: In a large Chinese cohort study two male patients with hemizygous FLNA missense mutations and spastic hemiplegic CP were identified. One additional patient in a cohort study of 52 patients with CP investigated for causative CNVs. This patient harbored a pathogenic maternally inherited triplication on Xq28 including FLNA. No information about the patient's gender is given.
One other cohort study (PMID 29706646) of patients with cortical malformations, which can be associated with CP overlapping features, also revealed one female patient with maternally inherited heterozygous FLNA mutation and ataxia. The mother had the same neuroradiologic features but did not show any symptoms.
Sources: Literature
Cerebral Palsy v1.36 FH Luisa Weiss gene: FH was added
gene: FH was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FH were set to 33528536; 27541980; 1432428
Phenotypes for gene: FH were set to Fumarase deficiency MIM#606812
Review for gene: FH was set to GREEN
Added comment: Two patients from a large CP cohort with biallelic (compound heterozygous) mutations in FH. Note that there is a recurrent mutation (NM_000143:c.1429_1430insAAA,p.K477delinsKK) which was already described in a compound heterozygous state in two sister with an attenuated form of fumarase deficiency and slowly progressive movement disorder (PMID:27541980).
One other case report of a girl with a previous diagnosis of cerebral palsy, nonprogressive
psychomotor retardation, and hypotonia and reduced fibroblast activity of FH to 10% and parental fibroblast activity of FH in the heterozygote range. No genetic testing had been performed on this patient.
Sources: Literature
Cerebral Palsy v1.36 ATM Luisa Weiss changed review comment from: 3 individuals presenting with CP and harboring biallelic compound heterozygous mutations in ATM. At least one the individual had an overlapping phenotype of CP with Ataxia Teleangiectasia
Sources: Literature; to: 3 individuals presenting with CP and harboring biallelic compound heterozygous mutations in ATM. At least one of the individual had an overlapping phenotype of CP with Ataxia Teleangiectasia
Sources: Literature
Cerebral Palsy v1.36 FARS2 Luisa Weiss gene: FARS2 was added
gene: FARS2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FARS2 were set to 33528536; 32989326; 25851414
Phenotypes for gene: FARS2 were set to Combined oxidative phosphorylation deficiency MIM#614946; 3 Spastic paraplegia MIM#617046
Review for gene: FARS2 was set to GREEN
Added comment: Four patients out of three publications (two large CP cohort studies with one patient each, one case report of two sibling with the clinical diagnosis of CP) with biallelic mutations in FARS2.
Sources: Literature
Cerebral Palsy v1.36 FAR1 Luisa Weiss gene: FAR1 was added
gene: FAR1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FAR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FAR1 were set to 33239752
Phenotypes for gene: FAR1 were set to Cataracts, spastic paraparesis, and speech delay MIM#619338
Mode of pathogenicity for gene: FAR1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: FAR1 was set to GREEN
Added comment: One publication with a total of 12 patients with an amino acid change at position 480 (p.Arg480Cys/His/Leu) of FAR1 and movement disorder, epilepsy and cataract. The movement disorder was non-progressive in almost all of the individuals even though the clinical diagnosis of CP was not given.
Functional studies in the same publication showed that patients with the heterozygous de novo variants have elevated levels of ether lipids, including plasmalogens, which makes these mutations gain-of-function mutations (in contrast to the peroxisomal fatty acyl-CoA reductase 1 disorder, which is caused by biallelic loss-of-function mutations in the same gene).
Sources: Literature
Cerebral Palsy v1.36 EEF1A2 Luisa Weiss gene: EEF1A2 was added
gene: EEF1A2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: EEF1A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EEF1A2 were set to 33528536; 30109124; 32196822
Phenotypes for gene: EEF1A2 were set to Developmental and epileptic encephalopathy MIM#616409
Review for gene: EEF1A2 was set to AMBER
Added comment: One patient in a large CP cohort with heterozygous EEF1A2 mutation. In another publication there is one patient from a cohort of patients with EIEE and EEF1A2 mutations that was also reported to have CP.
One other paper (PMID:32196822) presents a cohort of patients with epileptic-dyskinetic encephalopathy due to heterozygous de novo EEIF1A2 mutations of which 4 had a non-progressive movement disorder without the clinical diagnosis of CP.
Sources: Literature
Cerebral Palsy v1.36 ELP2 Luisa Weiss changed review comment from: Nine patients in two different publications described as having biallelic ELP2 mutations and a form of ID syndrome with cerebral palsy as one neurological feature. At least for one patient symptom progression was described.
Sources: Literature; to: Nine patients in two different publications described as having biallelic ELP2 mutations and a form of ID syndrome with cerebral palsy as one neurological feature. For one patient symptom progression was described.
Sources: Literature
Cerebral Palsy v1.36 ERCC8 Luisa Weiss changed review comment from: One large CP cohort study with 3 unrelated patients with biallelic mutations in ERCC8. Two were point mutations (one missense, one nonsense), the other a large deletion that included ERCC8 and NDUFAF2-gene. Another case report of a boy that was initially diagnosed as having CP but later re-diagnosed as having Cockayne syndrome due to biallelic ERCC8 mutations.
Sources: Literature; to: One large CP cohort study with 3 unrelated patients with biallelic mutations in ERCC8. Two were point mutations (one missense, one nonsense), the other a large deletion that included ERCC8 and NDUFAF2-gene. Another case report of a boy that was initially diagnosed as having CP but later re-diagnosed as having Cockayne syndrome due to biallelic ERCC8 mutations because of disease progression.
Sources: Literature
Cerebral Palsy v1.36 FAM126A Luisa Weiss gene: FAM126A was added
gene: FAM126A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FAM126A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM126A were set to 34788679
Phenotypes for gene: FAM126A were set to Leukodystrophy, hypomyelinating MIM#610532
Review for gene: FAM126A was set to AMBER
Added comment: One large CP cohort study with one patient with a homozygous HYCC1/FAM126A mutation and CP
Sources: Literature
Cerebral Palsy v1.36 EXOSC3 Luisa Weiss gene: EXOSC3 was added
gene: EXOSC3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: EXOSC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC3 were set to 33528536
Phenotypes for gene: EXOSC3 were set to Pontocerebellar hypoplasia MIM#614678
Review for gene: EXOSC3 was set to GREEN
Added comment: One large CP cohort study with 3 unrelated patients harboring the same homozygous missense mutation (p.D132A). The same missense mutation has been described in a homozygous state as well as compound heterozygous with a different pathogenic mutation in the same gene as causing pontocerebellar hypoplasia.
Sources: Literature
Cerebral Palsy v1.36 ERCC8 Luisa Weiss gene: ERCC8 was added
gene: ERCC8 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ERCC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC8 were set to 33528536; 30279719
Phenotypes for gene: ERCC8 were set to Cockayne syndrome MIM#216400
Review for gene: ERCC8 was set to GREEN
Added comment: One large CP cohort study with 3 unrelated patients with biallelic mutations in ERCC8. Two were point mutations (one missense, one nonsense), the other a large deletion that included ERCC8 and NDUFAF2-gene. Another case report of a boy that was initially diagnosed as having CP but later re-diagnosed as having Cockayne syndrome due to biallelic ERCC8 mutations.
Sources: Literature
Cerebral Palsy v1.36 ELP2 Luisa Weiss gene: ELP2 was added
gene: ELP2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ELP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ELP2 were set to 25131622; 33976153
Phenotypes for gene: ELP2 were set to Intellectual developmental disorder MIM#617270
Review for gene: ELP2 was set to GREEN
Added comment: Nine patients in two different publications described as having biallelic ELP2 mutations and a form of ID syndrome with cerebral palsy as one neurological feature. At least for one patient symptom progression was described.
Sources: Literature
Cerebral Palsy v1.36 DYRK1A Luisa Weiss gene: DYRK1A was added
gene: DYRK1A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DYRK1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DYRK1A were set to 33528536
Phenotypes for gene: DYRK1A were set to Intellectual developmental disorder MIM#614104
Review for gene: DYRK1A was set to GREEN
Added comment: 6 patients in one large CP cohort study described with mutations in DYRK1A.
Sources: Literature
Cerebral Palsy v1.36 DYNC1H1 Luisa Weiss gene: DYNC1H1 was added
gene: DYNC1H1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DYNC1H1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DYNC1H1 were set to 33528536; 25817843
Phenotypes for gene: DYNC1H1 were set to Charcot-Marie-Tooth disease MIM#614228; Cortical dysplasia, complex MIM#614563; Spinal muscular atrophy, lower extremity-predominant MIM#158600
Review for gene: DYNC1H1 was set to GREEN
Added comment: Four patients with de novo heterozygous missense mutations and one patient with a de novo gene deletion in DYNC1H1 in two independent CP cohort studies described.
Sources: Literature
Cerebral Palsy v1.36 DOCK6 Luisa Weiss gene: DOCK6 was added
gene: DOCK6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DOCK6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOCK6 were set to 25824905; 34114234
Phenotypes for gene: DOCK6 were set to Adams-Oliver syndrome 2 MIM#614219
Review for gene: DOCK6 was set to GREEN
Added comment: In one study (PMID:25824905) ten patients with Adams-Oliver syndrome type 2 were described, 4 of which had CP. All of them had ocular anomalies and scalp defects, indicating that there is a high phenotypic overlap with the autosomal recessive form of Adams-Oliver-syndrome that is associated with eye anomalies.
In another CP cohort study (PMID: 34114234) one patient with biallelic variants of unknown clinical significance in DOCK6 was described, but there was no indication of eye or skin anomalies.
Sources: Literature
Cerebral Palsy v1.36 CTNNA2 Luisa Weiss gene: CTNNA2 was added
gene: CTNNA2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CTNNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTNNA2 were set to 30013181
Phenotypes for gene: CTNNA2 were set to Cortical dysplasia, complex, with other brain malformations MIM#618174
Review for gene: CTNNA2 was set to GREEN
Added comment: In 7 affected individuals of three consanguineous families a complex brain malformation syndrome with pachygyria, cortical gray matter thickening, hypogenesis of the corpus callosum, and cerebellar hypoplasia, neurodevelopmental delay, acquired microcephaly and seizures is described. All of the individuals are described as having hypotonic cerebral palsy and biallelic mutations in CTNNA2.
Sources: Literature
Cerebral Palsy v1.36 CTBP1 Luisa Weiss gene: CTBP1 was added
gene: CTBP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTBP1 were set to 33528536
Phenotypes for gene: CTBP1 were set to Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome MIM#617915
Review for gene: CTBP1 was set to AMBER
Added comment: Two independent patients in one large CP cohort studies with the same mutations in this gene (p.R342W), both heterozygous, one of them confirmed de novo.

Another recurrent, possibly dominant negative functioning mutation described as causing an ID syndrome with ataxia, hypotonia and tooth enamel defects. Since there is no phenotype given in the CP cohort study, a possible phenotypic overlap cannot be ruled out.
Sources: Literature
Cerebral Palsy v1.36 CREBBP Luisa Weiss gene: CREBBP was added
gene: CREBBP was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CREBBP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CREBBP were set to 33528536; 34788679
Phenotypes for gene: CREBBP were set to Menke-Hennekam syndrome MIM#618332, Rubinstein-Taybi syndrome MIM#180849
Review for gene: CREBBP was set to GREEN
Added comment: 3 independent patients in 2 large CP cohort studies describes as having heterozygous de novo mutations in this gene. One mutation (PMID: 34788679) is a frameshift mutation, the two other mutations (PMID: 33528536) are missense mutations, one of which (p.M1872V) was already described twice in patients with Menke-Hennekam syndrome. Possible phenotypic overlap with ID syndrome.
Sources: Literature
Ataxia - paediatric v1.7 TPR Zornitza Stark Phenotypes for gene: TPR were changed from Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, TPR-related to Intellectual developmental disorder, autosomal recessive 79, MIM# 620393
Ataxia - paediatric v1.6 TPR Zornitza Stark edited their review of gene: TPR: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 79, MIM# 620393
Intellectual disability syndromic and non-syndromic v0.5230 TPR Zornitza Stark Phenotypes for gene: TPR were changed from Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, TPR-related to Intellectual developmental disorder, autosomal recessive 79, MIM# 620393
Intellectual disability syndromic and non-syndromic v0.5229 TPR Zornitza Stark edited their review of gene: TPR: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 79, MIM# 620393
Microcephaly v1.205 TPR Zornitza Stark Phenotypes for gene: TPR were changed from Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, TPR-related to Intellectual developmental disorder, autosomal recessive 79, MIM# 620393
Microcephaly v1.204 TPR Zornitza Stark edited their review of gene: TPR: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 79, MIM# 620393
Mendeliome v1.895 TPR Zornitza Stark Phenotypes for gene: TPR were changed from Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, TPR-related to Intellectual developmental disorder, autosomal recessive 79, MIM# 620393
Mendeliome v1.894 TPR Zornitza Stark edited their review of gene: TPR: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 79, MIM# 620393
Mendeliome v1.894 AMFR Zornitza Stark Marked gene: AMFR as ready
Mendeliome v1.894 AMFR Zornitza Stark Gene: amfr has been classified as Green List (High Evidence).
Mendeliome v1.894 AMFR Zornitza Stark Phenotypes for gene: AMFR were changed from Hereditary spastic paraplegia, MONDO:0019064 to Spastic paraplegia 89, autosomal recessive, MIM# 620379
Mendeliome v1.893 AMFR Zornitza Stark Classified gene: AMFR as Green List (high evidence)
Mendeliome v1.893 AMFR Zornitza Stark Gene: amfr has been classified as Green List (High Evidence).
Mendeliome v1.892 AMFR Zornitza Stark reviewed gene: AMFR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 89, autosomal recessive, MIM# 620379; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia - paediatric v1.63 AMFR Zornitza Stark Marked gene: AMFR as ready
Hereditary Spastic Paraplegia - paediatric v1.63 AMFR Zornitza Stark Gene: amfr has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.63 AMFR Zornitza Stark Phenotypes for gene: AMFR were changed from Hereditary spastic paraplegia, MONDO:0019064 to Spastic paraplegia 89, autosomal recessive, MIM# 620379
Hereditary Spastic Paraplegia - paediatric v1.62 AMFR Zornitza Stark Classified gene: AMFR as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v1.62 AMFR Zornitza Stark Gene: amfr has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.61 AMFR Zornitza Stark reviewed gene: AMFR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 89, autosomal recessive, MIM# 620379; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.892 ATP11A Zornitza Stark Classified gene: ATP11A as Green List (high evidence)
Mendeliome v1.892 ATP11A Zornitza Stark Gene: atp11a has been classified as Green List (High Evidence).
Mendeliome v1.891 ATP11A Zornitza Stark edited their review of gene: ATP11A: Added comment: PMID 35278131 reports three additional families with deafness, including segregation in a large pedigree.; Changed rating: GREEN; Changed publications: 35278131
Deafness_Isolated v1.46 ATP11A Zornitza Stark Phenotypes for gene: ATP11A were changed from Deafness, autosomal dominant 84 MIM#619810 to Deafness, autosomal dominant 84, MIM# 619810; Auditory neuropathy, autosomal dominant 2, MIM# 620384
Deafness_Isolated v1.45 ATP11A Zornitza Stark Publications for gene: ATP11A were set to 35278131
Deafness_Isolated v1.44 ATP11A Zornitza Stark Classified gene: ATP11A as Green List (high evidence)
Deafness_Isolated v1.44 ATP11A Zornitza Stark Gene: atp11a has been classified as Green List (High Evidence).
Deafness_Isolated v1.43 ATP11A Zornitza Stark reviewed gene: ATP11A: Rating: GREEN; Mode of pathogenicity: None; Publications: 35278131; Phenotypes: Deafness, autosomal dominant 84, MIM# 619810, Auditory neuropathy, autosomal dominant 2, MIM# 620384; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrops fetalis v0.298 RASA1 Lilian Downie reviewed gene: RASA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:36980822; Phenotypes: ?; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.149 CYP2U1 Sangavi Sivagnanasundram reviewed gene: CYP2U1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23176821; Phenotypes: Spastic paraplegia 56, autosomal recessive, MIM#615030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.149 CTDP1 Sangavi Sivagnanasundram reviewed gene: CTDP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 20301787; Phenotypes: Congenital cataracts, facial dysmorphism, and neuropathy (MIM#604168); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.149 COX10 Sangavi Sivagnanasundram reviewed gene: COX10: Rating: AMBER; Mode of pathogenicity: None; Publications: 10767350; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3 (MIM#619046); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.149 CNTNAP1 Sangavi Sivagnanasundram reviewed gene: CNTNAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29511323, 27881385; Phenotypes: Hypomyelinating neuropathy, congenital, 3 (MONDO:0017049, MIM#618186); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.149 BAG3 Sangavi Sivagnanasundram reviewed gene: BAG3: Rating: AMBER; Mode of pathogenicity: None; Publications: 19085932; Phenotypes: Myopathy, myofibrillar, 6 (MIM#612954, MONDO:0013061); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.36 COL4A1 Luisa Weiss reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536, 34531397; Phenotypes: Brain small vessel disease MIM#614483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.149 B4GALNT1 Sangavi Sivagnanasundram edited their review of gene: B4GALNT1: Changed rating: AMBER
Cerebral Palsy v1.36 CLTC Luisa Weiss gene: CLTC was added
gene: CLTC was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CLTC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLTC were set to 33528536; 31776469
Phenotypes for gene: CLTC were set to Intellectual developmental disorder MIM#617854
Review for gene: CLTC was set to GREEN
Added comment: One large CP cohort study with one patient reported.

One more publication with 13 cases of syndromic ID due to heterozygous CLTC mutations. Cerebral palsy affecting gait recurrently seen in these individuals.
Sources: Literature
Hereditary Neuropathy - complex v0.149 B4GALNT1 Sangavi Sivagnanasundram changed review comment from: Variable age of onset (typically during juvenile aged). Mutations in B4GALNT1 are known to be a rarer and more complicated form of SPG compared to other genes. (PMID: 20301682)

PMID: 23746551
5 unrelated families with gait abnormalities due to lower limb spasticity, hyperreflexia, extensor plantar responses, muscle weakness and atrophy, and mild to moderate intellectual disability.
All affected individuals in the families had homozygous mutations in B4GALNT1; to: Neuropathy is not a prominent feature in individuals

Variable age of onset (typically during juvenile aged). Mutations in B4GALNT1 are known to be a rarer and more complicated form of SPG compared to other genes. (PMID: 20301682)

PMID: 23746551
5 unrelated families with gait abnormalities due to lower limb spasticity, hyperreflexia, extensor plantar responses, muscle weakness and atrophy, and mild to moderate intellectual disability.
All affected individuals in the families had homozygous mutations in B4GALNT1
Hereditary Neuropathy - complex v0.149 B4GALNT1 Sangavi Sivagnanasundram edited their review of gene: B4GALNT1: Changed rating: RED
Cerebral Palsy v1.36 CLCN4 Luisa Weiss gene: CLCN4 was added
gene: CLCN4 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CLCN4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: CLCN4 were set to 34788679
Phenotypes for gene: CLCN4 were set to Raynaud-Claes syndrome MIM#300114
Review for gene: CLCN4 was set to AMBER
Added comment: One female patient presented in a large cohort study with phenotypic overlap to Raynaud-Claes syndrome (ID, epilepsy and language deficits). The mutation is a heterozygous missense mutation previously reported to cause Raynaud-Claes syndrome.
Sources: Literature
Hereditary Neuropathy - complex v0.149 B4GALNT1 Sangavi Sivagnanasundram reviewed gene: B4GALNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301682, 23746551; Phenotypes: Spastic paraplegia 26, autosomal recessive (MIM#609195, MONDO:0012213); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.36 ATP7B Luisa Weiss gene: ATP7B was added
gene: ATP7B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ATP7B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP7B were set to 34788679
Phenotypes for gene: ATP7B were set to Wilson disease MIM#277900
Review for gene: ATP7B was set to RED
Added comment: One reported case in a large CP cohort study with two mutations in ATP7B, however bi-parental inheritance was not confirmed. Low evidence for causality.
Sources: Literature
Cerebral Palsy v1.36 CHD8 Luisa Weiss gene: CHD8 was added
gene: CHD8 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CHD8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD8 were set to 33528536
Phenotypes for gene: CHD8 were set to Intellectual developmental disorder with autism and macrocephaly #615032
Review for gene: CHD8 was set to GREEN
Added comment: 3 individual cases in one large cohort study, two de novo missense mutations and one frameshift mutation with unknown inheritance.
Sources: Literature
Cerebral Palsy v1.36 CDKL5 Luisa Weiss gene: CDKL5 was added
gene: CDKL5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CDKL5 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: CDKL5 were set to 33528536; 34788679
Review for gene: CDKL5 was set to AMBER
Added comment: 2 individual cases in two independent large cohort studies. One mutation reported as a mosaic nonsense mutation, the other one reported as a de novo hemizygous frameshift mutation. No phenotype information given.
Sources: Literature
Cerebral Palsy v1.36 CASK Luisa Weiss gene: CASK was added
gene: CASK was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CASK was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: CASK were set to 33528536
Phenotypes for gene: CASK were set to Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749
Review for gene: CASK was set to GREEN
Added comment: 4 individual cases in one large CP cohort study. 3 of them confirmed de novo nonsense mutations, one in-frame five AA deletion with unknown inheritance. All reported to be heterozygous in an X-linked gene and thus affecting females as known for the allelic disease ID with pontine and cerebellar hypoplasia.
Sources: Literature
Cerebral Palsy v1.36 CACNA1A Luisa Weiss reviewed gene: CACNA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29761117, 33528536, 34364746, 34531397, 34788679; Phenotypes: Developmental and epileptic encephalopathy MIM#617106, Episodic ataxia MIM#108500, familial hemiplegic Migraine MIM#141500 and MIM#141500, Spinocerebellar ataxia MIM#183086; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.36 BRAT1 Luisa Weiss gene: BRAT1 was added
gene: BRAT1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: BRAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRAT1 were set to 29997391
Phenotypes for gene: BRAT1 were set to Neurodevelopmental disorder with cerebellar atrophy and with or without seizures MIM#618056; neonatal lethal rigidity and multifocal seizure syndrome MIM#614498
Review for gene: BRAT1 was set to AMBER
Added comment: Biallelic BRAT1 mutations cause a neurodevelopmental phenotype with evidence of marked genotype–phenotype correlation: homozygous null variants result in a severe phenotype, whereas compound heterozygosity for null/hypomorphic variants is associated with a milder phenotype. In one study one patient with homozygous hypomorphic variants was diagnosed as a congenital cerebral palsy due to spastic paraplegia.
Sources: Literature
Cerebral Palsy v1.36 BCL11A Luisa Weiss reviewed gene: BCL11A: Rating: GREEN; Mode of pathogenicity: None; Publications: 35856171, 33528536, 34077496; Phenotypes: Dias-Logan syndrome, MIM#617101; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia - adult onset v1.4 SCA27B Bryony Thompson Marked STR: SCA27B as ready
Ataxia - adult onset v1.4 SCA27B Bryony Thompson Str: sca27b has been classified as Green List (High Evidence).
Ataxia - adult onset v1.4 SCA27B Bryony Thompson Classified STR: SCA27B as Green List (high evidence)
Ataxia - adult onset v1.4 SCA27B Bryony Thompson Str: sca27b has been classified as Green List (High Evidence).
Ataxia - adult onset v1.3 SCA27B Bryony Thompson STR: SCA27B was added
STR: SCA27B was added to Ataxia - adult onset. Sources: Literature
Mode of inheritance for STR: SCA27B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA27B were set to 37165652; 36516086; 36493768
Phenotypes for STR: SCA27B were set to Spinocerebellar ataxia type 27B MONDO:0012247; Spinocerebellar ataxia 50; late-onset cerebellar ataxias (LOCAs)
Review for STR: SCA27B was set to GREEN
STR: SCA27B was marked as clinically relevant
Added comment: NM_175929.3(FGF14):c.208+239747CTT[X]
Expansions of 250 or more GAA repeat units were associated with late-onset cerebellar ataxia in a French-Canadian (OR: 105.60 [95% CI=31.09-334.20], p<0.001) and a German (OR: 8.76 [95% CI=3.45-20.84], p<0.001) case-control series. Additionally, expanded alleles greater than (GAA)332 are pathogenic and fully penetrant in a combined Australian and German dataset (p = 6.0 × 10−8, OR = 72 [95% CI = 4.3–1,227]). Whereas, alleles in the range of (GAA)250-334 are likely to be pathogenic with reduced penetrance (p = 0.0015, OR = 3.6 [95% CI = 1.6–7.9]).
250-300 repeats in the incompletely penetrant range
>300 is fully penetrant for ataxia
Sources: Literature
Repeat Disorders v0.153 SCA27B Bryony Thompson Marked STR: SCA27B as ready
Repeat Disorders v0.153 SCA27B Bryony Thompson Str: sca27b has been classified as Green List (High Evidence).
Repeat Disorders v0.153 SCA27B Bryony Thompson Classified STR: SCA27B as Green List (high evidence)
Repeat Disorders v0.153 SCA27B Bryony Thompson Str: sca27b has been classified as Green List (High Evidence).
Repeat Disorders v0.152 SCA27B Bryony Thompson STR: SCA27B was added
STR: SCA27B was added to Repeat Disorders. Sources: Literature
Mode of inheritance for STR: SCA27B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA27B were set to 37165652; 36516086; 36493768
Phenotypes for STR: SCA27B were set to Spinocerebellar ataxia type 27B MONDO:0012247; Spinocerebellar ataxia 50; late-onset cerebellar ataxias (LOCAs)
Review for STR: SCA27B was set to GREEN
STR: SCA27B was marked as clinically relevant
Added comment: NM_175929.3(FGF14):c.208+239747CTT[X]
Expansions of 250 or more GAA repeat units were associated with late-onset cerebellar ataxia in a French-Canadian (OR: 105.60 [95% CI=31.09-334.20], p<0.001) and a German (OR: 8.76 [95% CI=3.45-20.84], p<0.001) case-control series. Additionally, expanded alleles greater than (GAA)332 are pathogenic and fully penetrant in a combined Australian and German dataset (p = 6.0 × 10−8, OR = 72 [95% CI = 4.3–1,227]). Whereas, alleles in the range of (GAA)250-334 are likely to be pathogenic with reduced penetrance (p = 0.0015, OR = 3.6 [95% CI = 1.6–7.9]).
250-300 repeats in the incompletely penetrant range
>300 is fully penetrant for ataxia
Sources: Literature
Cerebral Palsy v1.36 ATP8A2 Luisa Weiss gene: ATP8A2 was added
gene: ATP8A2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ATP8A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP8A2 were set to 35321980; 30542205; 34077496
Phenotypes for gene: ATP8A2 were set to Cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome, MIM#615268
Review for gene: ATP8A2 was set to GREEN
Added comment: 4 individuals from 3 families with biallelic mutations in ATP8A2 and CP. 3/4 patients presented with intellectual disability.

PMID 35321980: Two sibling reported with a non-progressive dyskinetic cerebral palsy resembling cerebellar ataxia (athetotic movements, ptosis, ophthalmoplegia, hypotonia, delayed development)

PMID 30542205: One patient with atypical CP (atypical due to intellectual disability)because intell dis and typical neurologic pattern (hypertonia, ataxia or transient episodic exacerbations of neurologic symptoms)

PMID 34077496: One patient with CP and microcephaly likely due to simultaneously present biallelic CIT mutations
Sources: Literature
Cerebral Palsy v1.36 ATP7A Luisa Weiss gene: ATP7A was added
gene: ATP7A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ATP7A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ATP7A were set to 35322241; 33528536; 34788679
Phenotypes for gene: ATP7A were set to Menkes disease MIM#3094009
Review for gene: ATP7A was set to GREEN
Added comment: 3 individuals from 3 different publications with CP. Two patients were male with de novo splice affecting mutations. One patient was female with a heterozygous de novo frameshift mutation in ATP7B causative for the disease as described before for Menkes disease.
Sources: Literature
Cerebral Palsy v1.36 ATM Luisa Weiss gene: ATM was added
gene: ATM was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ATM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATM were set to 34364746; 26380989; 34114234
Phenotypes for gene: ATM were set to Ataxia-telangiectasia, MIM#208900
Review for gene: ATM was set to GREEN
Added comment: 3 individuals presenting with CP and harboring biallelic compound heterozygous mutations in ATM. At least one the individual had an overlapping phenotype of CP with Ataxia Teleangiectasia
Sources: Literature
Cerebral Palsy v1.36 ARID2 Luisa Weiss gene: ARID2 was added
gene: ARID2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ARID2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARID2 were set to 33528536
Phenotypes for gene: ARID2 were set to Coffin-Siris syndrome, MIM#617808
Review for gene: ARID2 was set to GREEN
Added comment: Large cohort study with three individual cases with CP and de novo ARID2 mutations (2 nonsense and 1 frameshift mutation)
Sources: Literature
Cerebral Palsy v1.36 ARG1 Luisa Weiss gene: ARG1 was added
gene: ARG1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ARG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARG1 were set to 35505270; 34788679
Phenotypes for gene: ARG1 were set to Argininemia MIM#207800
Review for gene: ARG1 was set to GREEN
Added comment: Literature review: Three independent cases have been published with biallelic mutations in ARG1 and presenting with cerebral palsy. Two patients harbored a recurrent splice site mutation, one patient presented with compound heterozygous missense mutations.
Sources: Literature
Mendeliome v1.891 SCN4A Zornitza Stark Phenotypes for gene: SCN4A were changed from Hyperkalemic periodic paralysis, type 2, MIM# 170500; Hypokalemic periodic paralysis, type 2, MIM# 613345; Myasthenic syndrome, congenital, 16, MIM# 614198; Myotonia congenita, atypical, acetazolamide-responsive , MIM#608390; Paramyotonia congenita , MIM#168300 to Congenital myopathy 22A, classic, MIM# 620351; Congenital myopathy 22B, severe fetal, MIM# 620369; Hyperkalemic periodic paralysis, type 2, MIM# 170500; Hypokalemic periodic paralysis, type 2, MIM# 613345; Myasthenic syndrome, congenital, 16, MIM# 614198; Myotonia congenita, atypical, acetazolamide-responsive , MIM#608390; Paramyotonia congenita , MIM#168300
Mendeliome v1.890 SCN4A Zornitza Stark edited their review of gene: SCN4A: Changed phenotypes: Congenital myopathy 22A, classic, MIM# 620351, Congenital myopathy 22B, severe fetal, MIM# 620369, Hyperkalemic periodic paralysis, type 2, MIM# 170500, Hypokalemic periodic paralysis, type 2, MIM# 613345, Myasthenic syndrome, congenital, 16, MIM# 614198, Myotonia congenita, atypical, acetazolamide-responsive , MIM#608390, Paramyotonia congenita , MIM#168300
Fetal anomalies v1.108 SCN4A Zornitza Stark Phenotypes for gene: SCN4A were changed from Congenital myopathy; Myasthenic syndrome, congenital, 16 MIM#614198 to Congenital myopathy 22B, severe fetal, MIM# 620369; Myasthenic syndrome, congenital, 16 MIM#614198
Fetal anomalies v1.107 SCN4A Zornitza Stark reviewed gene: SCN4A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital myopathy 22B, severe fetal, MIM# 620369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Tubulopathies and related disorders v1.9 OXGR1 Zornitza Stark Phenotypes for gene: OXGR1 were changed from Nephrolithiasis/nephrocalcinosis, MONDO:0008171, OXGR1-related to Nephrolithiasis, calcium oxalate, 2, with nephrocalcinosis, MIM# 620374
Renal Tubulopathies and related disorders v1.8 OXGR1 Zornitza Stark reviewed gene: OXGR1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephrolithiasis, calcium oxalate, 2, with nephrocalcinosis, MIM# 620374; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.890 OXGR1 Zornitza Stark Phenotypes for gene: OXGR1 were changed from Nephrolithiasis/nephrocalcinosis MONDO:0008171, OXGR1-related to Nephrolithiasis, calcium oxalate, 2, with nephrocalcinosis, MIM# 620374
Mendeliome v1.889 OXGR1 Zornitza Stark reviewed gene: OXGR1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephrolithiasis, calcium oxalate, 2, with nephrocalcinosis, MIM# 620374; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.36 AKT3 Luisa Weiss gene: AKT3 was added
gene: AKT3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: AKT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AKT3 were set to 34354878; 30542205; 32989326
Review for gene: AKT3 was set to AMBER
Added comment: Two individual patients with CP and an AKT3 mutation have been published. In one of them (PMID 34354878) CP might be caused by birth asphyxia and is not be related to the AKT3 mutation. Additionally, there is functional data supporting the hypothesis that AKT3 might be a causative gene (PMID 32989326).

PMID 34354878: One patient described as presenting with MPPH and having a mutation in AKT3, while the mutation itself is not named (unknown whether LoF or missense, de novo or inherited). CP is listed as a coexisting feature in this patient which was caused by birth asphyxia due to umbilical cord strangulation around his neck.

30542205: One additional case with atypical CP (atypical due to major brain malformations and progressive neurologic disease) and a de novo missense mutation
Sources: Literature
Disorders of immune dysregulation v0.174 LYN Zornitza Stark Marked gene: LYN as ready
Disorders of immune dysregulation v0.174 LYN Zornitza Stark Gene: lyn has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.174 LYN Zornitza Stark Classified gene: LYN as Green List (high evidence)
Disorders of immune dysregulation v0.174 LYN Zornitza Stark Gene: lyn has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.173 LYN Zornitza Stark gene: LYN was added
gene: LYN was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: LYN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LYN were set to 36932076; 36122175
Phenotypes for gene: LYN were set to Autoinflammatory disease, systemic, with vasculitis, MIM# 620376
Review for gene: LYN was set to GREEN
Added comment: Three unrelated individuals from described with three distinct de novo variants in LYN, p.Y508*, p.Q507* and a missense variant, p.Y508F. The PTC variants do not cause NMD, and all three variants have been shown to result in constitutively active LYN kinase by preventing inhibitory phosphorylation of the Y508 regulatory tyrosine. Extensive functional data to confirm gain-of-function effect was presented. Patient presented perinatally with immunological symptoms, including diffuse purpuric skin lesions, fever, and increased C-reactive protein (CRP). mild anemia, mild leukocytosis, moderate to severe thrombocytopenia. The patients with PTC were more severe, developing liver fibrosis and signs of cirrhosis. All three patients responded to various degrees to treatment with src kinase inhibitors, dasatinib, etanercept and/or colchicine. Authors named the condition Lyn kinase-associated vasculopathy and liver fibrosis (LAVLI). A fourth patient with a Tyr508His has also been described and presented with since birth with recurrent fever, chronic urticaria, atopic dermatitis, arthralgia, increased inflammatory biomarkers, and elevated plasma cytokine levels. Other features not consistent with LYN disease were attributed to prematurity (following maternal HELLP syndrome) and potentially other genetic factors.
Sources: Literature
Mendeliome v1.889 LYN Zornitza Stark Phenotypes for gene: LYN were changed from Vasculitis, MONDO:0018882, LYN-related to Autoinflammatory disease, systemic, with vasculitis, MIM# 620376
Mendeliome v1.888 LYN Zornitza Stark edited their review of gene: LYN: Changed phenotypes: Autoinflammatory disease, systemic, with vasculitis, MIM# 620376
Vasculitis v0.80 LYN Zornitza Stark Phenotypes for gene: LYN were changed from Vasculitis, MONDO:0018882, LYN-related to Autoinflammatory disease, systemic, with vasculitis, MIM# 620376
Vasculitis v0.79 LYN Zornitza Stark reviewed gene: LYN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammatory disease, systemic, with vasculitis, MIM# 620376; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.36 AHDC1 Luisa Weiss gene: AHDC1 was added
gene: AHDC1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: AHDC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AHDC1 were set to 33528536
Phenotypes for gene: AHDC1 were set to Xia-Gibbs syndrome, MIM#615829
Review for gene: AHDC1 was set to GREEN
Added comment: 3 individuals in CP cohort with mono-allelic de novo variants (2 frameshift, 1 6-AA-deletion).

Other ADHC1 frameshift mutations have been known to cause an early onset neurological disorder with absent or poor expressive language, obstructive sleep apnea and brain abnormalities.
Sources: Literature
Cerebral Palsy v1.36 ADNP Luisa Weiss gene: ADNP was added
gene: ADNP was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ADNP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADNP were set to 33528536
Phenotypes for gene: ADNP were set to Helsmoortel-van der Aa syndrome MIM#615873
Review for gene: ADNP was set to AMBER
Added comment: Large cohort study of cerebral palsy cases identified two variants in two individual patients with CP. One mutation was a recurrent Helsmoortel-van der Aa-syndrome nonsense mutation, the other was a de novo frameshift mutation. No further information about the patient's phenotype was given.
Sources: Literature
Cerebral Palsy v1.36 ACADM Luisa Weiss gene: ACADM was added
gene: ACADM was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ACADM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACADM were set to 11263545; 35076175
Phenotypes for gene: ACADM were set to Acyl-CoA dehydrogenase, medium chain, deficiency of, MIM# 201450
Review for gene: ACADM was set to AMBER
Added comment: Currently unclear if variants in this gene can cause CP. If so, CP is likely to happen as a secondary effect of the brain damage happening if Acyl-CoA dehydrogenase deficiency is not treated correctly or early enough.
According to one study, CP can be present in 9% of cases with biallelic mutations in ACADM, probably secondary to the underlying disease and associated with early-onset seizures (PMID 11263545).
In a second publication one other case of CP associated with biallelic mutations in ACADM was presented, but this patient's phenotype was likely caused by biallelic mutations in PDHX which were present simultaneously.
Sources: Literature
Hereditary Neuropathy - complex v0.149 APTX Sangavi Sivagnanasundram reviewed gene: APTX: Rating: GREEN; Mode of pathogenicity: None; Publications: 11586299; Phenotypes: Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia (MIM#208920); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.888 NDUFA13 Zornitza Stark Classified gene: NDUFA13 as Green List (high evidence)
Mendeliome v1.888 NDUFA13 Zornitza Stark Gene: ndufa13 has been classified as Green List (High Evidence).
Mitochondrial disease v0.874 NDUFA13 Zornitza Stark Classified gene: NDUFA13 as Green List (high evidence)
Mitochondrial disease v0.874 NDUFA13 Zornitza Stark Gene: ndufa13 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.156 SLC52A3 Zornitza Stark Marked gene: SLC52A3 as ready
Motor Neurone Disease v0.156 SLC52A3 Zornitza Stark Gene: slc52a3 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.156 SLC52A3 Zornitza Stark Phenotypes for gene: SLC52A3 were changed from to Amytrophic Lateral Sclerosis (ALS); Brown-Vialetto-van Laere syndrome 1 (MIM# 211530)
Motor Neurone Disease v0.155 SLC52A3 Zornitza Stark Publications for gene: SLC52A3 were set to
Motor Neurone Disease v0.154 SLC52A3 Zornitza Stark Mode of inheritance for gene: SLC52A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.153 TARDBP Zornitza Stark Marked gene: TARDBP as ready
Motor Neurone Disease v0.153 TARDBP Zornitza Stark Gene: tardbp has been classified as Green List (High Evidence).
Motor Neurone Disease v0.153 TARDBP Zornitza Stark Phenotypes for gene: TARDBP were changed from to Amyotrophic lateral sclerosis 10, with or without FTD; Frontotemporal lobar degeneration, TARDBP-related (MIM#612069; MONDO: 0012790)
Motor Neurone Disease v0.152 TARDBP Zornitza Stark Publications for gene: TARDBP were set to
Motor Neurone Disease v0.151 TARDBP Zornitza Stark Mode of inheritance for gene: TARDBP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.150 TBK1 Zornitza Stark Marked gene: TBK1 as ready
Motor Neurone Disease v0.150 TBK1 Zornitza Stark Gene: tbk1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.150 TBK1 Zornitza Stark Phenotypes for gene: TBK1 were changed from to Amyotrophic lateral sclerosis 4 (MIM#616439; MONDO:0011223)
Motor Neurone Disease v0.149 TBK1 Zornitza Stark Publications for gene: TBK1 were set to
Motor Neurone Disease v0.148 TBK1 Zornitza Stark Mode of inheritance for gene: TBK1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.147 UBQLN2 Zornitza Stark Marked gene: UBQLN2 as ready
Motor Neurone Disease v0.147 UBQLN2 Zornitza Stark Gene: ubqln2 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.147 UBQLN2 Zornitza Stark Phenotypes for gene: UBQLN2 were changed from to Amyotrophic lateral sclerosis type 15 (MONDO:0010459; MIM#300857)
Motor Neurone Disease v0.146 UBQLN2 Zornitza Stark Publications for gene: UBQLN2 were set to
Motor Neurone Disease v0.145 UBQLN2 Zornitza Stark Mode of inheritance for gene: UBQLN2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Motor Neurone Disease v0.144 VAPB Zornitza Stark Marked gene: VAPB as ready
Motor Neurone Disease v0.144 VAPB Zornitza Stark Gene: vapb has been classified as Green List (High Evidence).
Motor Neurone Disease v0.144 VAPB Zornitza Stark Phenotypes for gene: VAPB were changed from to Spinal muscular atrophy, late-onset, Finkel type (MIM# 182980); Amyotrophic lateral sclerosis 8
Motor Neurone Disease v0.143 VAPB Zornitza Stark Publications for gene: VAPB were set to
Motor Neurone Disease v0.142 VAPB Zornitza Stark Mode of inheritance for gene: VAPB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.141 VAPB Zornitza Stark Tag founder tag was added to gene: VAPB.
Motor Neurone Disease v0.141 VCP Zornitza Stark Marked gene: VCP as ready
Motor Neurone Disease v0.141 VCP Zornitza Stark Gene: vcp has been classified as Green List (High Evidence).
Motor Neurone Disease v0.141 VCP Zornitza Stark Phenotypes for gene: VCP were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 (ALS) (MIM#613954)
Motor Neurone Disease v0.140 VCP Zornitza Stark Publications for gene: VCP were set to
Motor Neurone Disease v0.139 VCP Zornitza Stark Mode of inheritance for gene: VCP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.149 ABCD1 Zornitza Stark Marked gene: ABCD1 as ready
Hereditary Neuropathy - complex v0.149 ABCD1 Zornitza Stark Gene: abcd1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.149 ABCD1 Zornitza Stark Phenotypes for gene: ABCD1 were changed from Adrenomyeloneuropathy, spastic paraparesis, adrenal insufficiency, axonal sensory-motor neuropathy, sphincter disturbance to Adrenomyeloneuropathy, adult (MIM#300100); Adrenomyeloneuropathy, spastic paraparesis, adrenal insufficiency, axonal sensory-motor neuropathy, sphincter disturbance
Hereditary Neuropathy - complex v0.148 ABCD1 Zornitza Stark Publications for gene: ABCD1 were set to
Hereditary Neuropathy - complex v0.147 AFG3L2 Zornitza Stark Marked gene: AFG3L2 as ready
Hereditary Neuropathy - complex v0.147 AFG3L2 Zornitza Stark Gene: afg3l2 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.147 AFG3L2 Zornitza Stark Phenotypes for gene: AFG3L2 were changed from Early-onset spastic paraplegia, later myoclonic epilepsy, sensory-motor axonal neuropathy, ataxia, dystonia to Spastic ataxia 5, autosomal recessive, MIM# 614487, MONDO:0013776; Early-onset spastic paraplegia, later myoclonic epilepsy, sensory-motor axonal neuropathy, ataxia, dystonia
Hereditary Neuropathy - complex v0.146 AFG3L2 Zornitza Stark Publications for gene: AFG3L2 were set to
Hereditary Neuropathy - complex v0.145 AFG3L2 Zornitza Stark Mode of inheritance for gene: AFG3L2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.144 AFG3L2 Zornitza Stark reviewed gene: AFG3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic ataxia 5, autosomal recessive, MIM# 614487; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.144 AMACR Zornitza Stark Marked gene: AMACR as ready
Hereditary Neuropathy - complex v0.144 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.144 AMACR Zornitza Stark Phenotypes for gene: AMACR were changed from Retinopathy, myelopathy, axonal or SNCV neuropathy, elevated phytanic and pristanic acids to Alpha-methylacyl-CoA racemase deficiency (MIM#614307); Retinopathy, myelopathy, axonal or SNCV neuropathy, elevated phytanic and pristanic acids
Hereditary Neuropathy - complex v0.143 AMACR Zornitza Stark Publications for gene: AMACR were set to
Miscellaneous Metabolic Disorders v1.27 Bryony Thompson removed gene:PINK1 from the panel
Mitochondrial disease v0.873 PINK1 Bryony Thompson Marked gene: PINK1 as ready
Mitochondrial disease v0.873 PINK1 Bryony Thompson Gene: pink1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.873 PINK1 Bryony Thompson Phenotypes for gene: PINK1 were changed from to Parkinson disease 6, early onset, MIM# 605909
Mitochondrial disease v0.872 PINK1 Bryony Thompson Publications for gene: PINK1 were set to
Mitochondrial disease v0.871 PINK1 Bryony Thompson Classified gene: PINK1 as Green List (high evidence)
Mitochondrial disease v0.871 PINK1 Bryony Thompson Added comment: Comment on list classification: ICIMD Nosology Group
Disorders of mitochondrial protein quality control
Mitochondrial disease v0.871 PINK1 Bryony Thompson Gene: pink1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.869 PINK1 Bryony Thompson gene: PINK1 was added
gene: PINK1 was added to Mitochondrial disease. Sources: Expert list
Mode of inheritance for gene: PINK1 was set to BIALLELIC, autosomal or pseudoautosomal
Macular Dystrophy/Stargardt Disease v0.43 CDHR1 Bryony Thompson Marked gene: CDHR1 as ready
Macular Dystrophy/Stargardt Disease v0.43 CDHR1 Bryony Thompson Gene: cdhr1 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.43 CDHR1 Bryony Thompson Classified gene: CDHR1 as Green List (high evidence)
Macular Dystrophy/Stargardt Disease v0.43 CDHR1 Bryony Thompson Gene: cdhr1 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.42 CDHR1 Bryony Thompson gene: CDHR1 was added
gene: CDHR1 was added to Macular Dystrophy/Stargardt Disease. Sources: Expert list
Mode of inheritance for gene: CDHR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDHR1 were set to 32681094; 31387115; 35627310
Phenotypes for gene: CDHR1 were set to Genetic macular dystrophy MONDO:0020242
Review for gene: CDHR1 was set to GREEN
gene: CDHR1 was marked as current diagnostic
Added comment: >10 individuals with late-onset macular dystrophy reported, mainly with c.783G>A (synonymous variant leading to in-frame skipping of exon 8) in the homozygous state or compound heterozygous with a second pathogenic variant in CDHR1
Sources: Expert list
Hereditary Neuropathy - complex v0.142 AMACR Sangavi Sivagnanasundram reviewed gene: AMACR: Rating: GREEN; Mode of pathogenicity: None; Publications: 36108118, 10655068, 20821052, 18032455; Phenotypes: Alpha-methylacyl-CoA racemase deficiency (MIM#614307); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.142 AFG3L2 Sangavi Sivagnanasundram reviewed gene: AFG3L2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 22022284, 25401298; Phenotypes: Spastic Ataxia 5 (MIM#614487, MONDO:0013776); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.240 GIGYF2 Bryony Thompson Publications for gene: GIGYF2 were set to 18358451; 33239198; 25279164; 20060621; 19250854; 26152800; 19449032
Early-onset Parkinson disease v0.239 GIGYF2 Bryony Thompson Publications for gene: GIGYF2 were set to PMID: 18358451, 19449032
Early-onset Parkinson disease v0.238 GIGYF2 Bryony Thompson Classified gene: GIGYF2 as Red List (low evidence)
Early-onset Parkinson disease v0.238 GIGYF2 Bryony Thompson Gene: gigyf2 has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.237 GIGYF2 Bryony Thompson reviewed gene: GIGYF2: Rating: RED; Mode of pathogenicity: None; Publications: 18358451, 33239198, 25279164, 20060621, 19250854, 26152800; Phenotypes: {Parkinson disease 11} , OMIM # 607688; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.887 GIGYF2 Bryony Thompson Publications for gene: GIGYF2 were set to PMID: 18358451, 19449032
Mendeliome v1.886 GIGYF2 Bryony Thompson Classified gene: GIGYF2 as Red List (low evidence)
Mendeliome v1.886 GIGYF2 Bryony Thompson Gene: gigyf2 has been classified as Red List (Low Evidence).
Mendeliome v1.885 GIGYF2 Bryony Thompson reviewed gene: GIGYF2: Rating: RED; Mode of pathogenicity: None; Publications: 18358451, 33239198, 25279164, 20060621, 19250854, 26152800; Phenotypes: {Parkinson disease 11} , OMIM # 607688; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.142 ABCD1 Sangavi Sivagnanasundram reviewed gene: ABCD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301491; Phenotypes: Adrenomyeloneuropathy, adult (MIM#300100); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Motor Neurone Disease v0.138 VCP Sangavi Sivagnanasundram reviewed gene: VCP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301649, 20301623, 21145000; Phenotypes: Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 (ALS) (MIM#613954); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.138 VAPB Sangavi Sivagnanasundram reviewed gene: VAPB: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301623, 15372378; Phenotypes: Spinal muscular atrophy, late-onset, Finkel type (MIM# 182980), Amyotrophic lateral sclerosis 8; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v1.66 CDC45 Zornitza Stark Publications for gene: CDC45 were set to 27374770
Craniosynostosis v1.65 MAN2B1 Zornitza Stark Marked gene: MAN2B1 as ready
Craniosynostosis v1.65 MAN2B1 Zornitza Stark Gene: man2b1 has been classified as Green List (High Evidence).
Craniosynostosis v1.65 MAN2B1 Zornitza Stark Classified gene: MAN2B1 as Green List (high evidence)
Craniosynostosis v1.65 MAN2B1 Zornitza Stark Gene: man2b1 has been classified as Green List (High Evidence).
Craniosynostosis v1.64 IL6ST Zornitza Stark Marked gene: IL6ST as ready
Craniosynostosis v1.64 IL6ST Zornitza Stark Gene: il6st has been classified as Amber List (Moderate Evidence).
Craniosynostosis v1.64 IL6ST Zornitza Stark Classified gene: IL6ST as Amber List (moderate evidence)
Craniosynostosis v1.64 IL6ST Zornitza Stark Gene: il6st has been classified as Amber List (Moderate Evidence).
Craniosynostosis v1.63 FBXO11 Zornitza Stark Marked gene: FBXO11 as ready
Craniosynostosis v1.63 FBXO11 Zornitza Stark Gene: fbxo11 has been classified as Green List (High Evidence).
Craniosynostosis v1.63 FBXO11 Zornitza Stark Classified gene: FBXO11 as Green List (high evidence)
Craniosynostosis v1.63 FBXO11 Zornitza Stark Gene: fbxo11 has been classified as Green List (High Evidence).
Craniosynostosis v1.62 KAT6B Zornitza Stark Marked gene: KAT6B as ready
Craniosynostosis v1.62 KAT6B Zornitza Stark Gene: kat6b has been classified as Green List (High Evidence).
Craniosynostosis v1.62 KAT6B Zornitza Stark Classified gene: KAT6B as Green List (high evidence)
Craniosynostosis v1.62 KAT6B Zornitza Stark Gene: kat6b has been classified as Green List (High Evidence).
Motor Neurone Disease v0.138 UBQLN2 Sangavi Sivagnanasundram reviewed gene: UBQLN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301623, 21857683; Phenotypes: Amyotrophic lateral sclerosis type 15 (MONDO:0010459, MIM#300857); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Incidentalome v0.230 UBQLN2 Sangavi Sivagnanasundram edited their review of gene: UBQLN2: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Incidentalome v0.230 UBQLN2 Sangavi Sivagnanasundram changed review comment from: Established gene identified in many individuals with ALS and/or dementia however there is conflicting evidence on the mode of pathogenicity.

PMID: 21857683 – 3 unrelated individuals with missense mutations (P497S, P509S, P525S) causative of UBQLN2- related ALS and ALS/Dementia.

PMID: 31319884 Reports on multiple articles conducting functional studies with evidence supporting that mutations in UBQLN2 impair the UPS pathway.

PMID: 26152284 – In vivo mouse model that showed that UBQLN2 mutants cause neurodegeneration and aggregate formation however the gene-disease association link wasn’t identified.

PMID: 25388785 – transgenic knockout rat model showed that mutant UBQLN2 cells lead to aggregation formation. Cresyl violet staining in the rats showed a reduction in neuron density which led to neurodegeneration. Neural impairment in the rats were confirmed by Golgi staining and was shown to have a distorted structure of cortex.; to: Established gene identified in many individuals with ALS and/or dementia however there is conflicting evidence on the mode of pathogenicity.

PMID: 21857683 – 3 unrelated individuals with missense mutations (P497S, P509S, P525S) causative of UBQLN2- related ALS and ALS/Dementia.

PMID: 31319884 Reports on multiple articles conducting functional studies with evidence supporting that mutations in UBQLN2 impair the UPS pathway.

PMID: 26152284 – In vivo mouse model that showed that UBQLN2 mutants cause neurodegeneration and aggregate formation however the gene-disease association link wasn’t identified.

PMID: 25388785 – transgenic knockout rat model showed that mutant UBQLN2 cells lead to aggregation formation. Cresyl violet staining in the rats showed a reduction in neuron density which led to neurodegeneration. Neural impairment in the rats were confirmed by Golgi staining and was shown to have a distorted structure of cortex.
Motor Neurone Disease v0.138 TBK1 Sangavi Sivagnanasundram reviewed gene: TBK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301623, 25803835; Phenotypes: Amyotrophic lateral sclerosis 4 (MIM#616439, mMONDO:0011223); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.138 TARDBP Sangavi Sivagnanasundram reviewed gene: TARDBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301761, 18309045, 19609911; Phenotypes: Amyotrophic lateral sclerosis 10, with or without FTD, Frontotemporal lobar degeneration, TARDBP-related (MIM#612069, MONDO: 0012790); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.138 SLC52A3 Sangavi Sivagnanasundram reviewed gene: SLC52A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26072523; Phenotypes: Amytrophic Lateral Sclerosis (ALS), Brown-Vialetto-van Laere syndrome 1 (MIM# 211530); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.138 SLC52A2 Sangavi Sivagnanasundram changed review comment from: Well established gene causative of ALS - Phenotypic features typically seen with an early age of onset (within the first few years of life)

PMID: 22864630
HEK293 in vitro functional assay was conducted that showed the reduced transporter activity compared to the wildtype in the presence of a SLC52A2 mutation.; to: Well established gene with overlapping phenotypic features consistent with ALS - Phenotypic features typically seen with an early age of onset (within the first few years of life)

PMID: 22864630
HEK293 in vitro functional assay was conducted that showed the reduced transporter activity compared to the wildtype in the presence of a SLC52A2 mutation.
Motor Neurone Disease v0.138 SLC52A2 Sangavi Sivagnanasundram reviewed gene: SLC52A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26072523, 22864630, 22740598, 20206331, 21110228; Phenotypes: Amyotrophic lateral sclerosis (ALS), Brown-Vialetto-van Laere syndrome 2 (MIM#614707) (BVVLS2); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.138 SIGMAR1 Sangavi Sivagnanasundram reviewed gene: SIGMAR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26078401; Phenotypes: ?Spinal muscular atrophy, distal, autosomal recessive, 2 (MIM#605726); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.138 SETX Sangavi Sivagnanasundram reviewed gene: SETX: Rating: GREEN; Mode of pathogenicity: None; Publications: 15106121, 9497266; Phenotypes: Amyotrophic Lateral Sclerosis 4, juvenile (MIM#602433); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Motor Neurone Disease v0.138 OPTN Sangavi Sivagnanasundram reviewed gene: OPTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20428114, 31838784, 27493188; Phenotypes: Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia (MONDO: 0013264, MIM#613435); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Motor Neurone Disease v0.138 FUS Sangavi Sivagnanasundram reviewed gene: FUS: Rating: GREEN; Mode of pathogenicity: None; Publications: 19251628, 19251627; Phenotypes: Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia (MIM#608030); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.138 ASCC1 Sangavi Sivagnanasundram reviewed gene: ASCC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26924529, 28218388; Phenotypes: spinal muscular atrophy with congenital bone fractures 2 (MONDO:0014807, MIM#616867); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.885 NDUFA13 Lucy Spencer reviewed gene: NDUFA13: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 28, MIM# 618249; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mitochondrial disease v0.868 NDUFA13 Lucy Spencer reviewed gene: NDUFA13: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 28, MIM# 618249; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1851 UNC13A Ain Roesley Marked gene: UNC13A as ready
Genetic Epilepsy v0.1851 UNC13A Ain Roesley Gene: unc13a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1851 UNC13A Ain Roesley Classified gene: UNC13A as Green List (high evidence)
Genetic Epilepsy v0.1851 UNC13A Ain Roesley Gene: unc13a has been classified as Green List (High Evidence).
Autism v0.188 UNC13A Ain Roesley commented on gene: UNC13A
Genetic Epilepsy v0.1850 UNC13A Ain Roesley gene: UNC13A was added
gene: UNC13A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: UNC13A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UNC13A were set to 28192369
Phenotypes for gene: UNC13A were set to neurodevelopmental disorder MONDO#0700092, UNC13A-related
Penetrance for gene: UNC13A were set to Complete
Review for gene: UNC13A was set to GREEN
gene: UNC13A was marked as current diagnostic
Added comment: Total of 3 probands with de novo Pro814Leu

Clinvar (believed to be a different proband reported in Lipstein 2017 in whom regression was never observed) :
Delayed speech and language development, Cerebellar ataxia, Tremor, Febrile seizure (within the age range of 3 months to 6 years), Developmental regression

VCGS internal cohort:
GDD, speech apraxia, febrile seizures, tremor, aortic root aneurysm, dilatation of the renal pelvis and Arnold-Chiari type I malformation

Lipstein 2017:
abnormal movements, developmental delay and autism
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5229 UNC13A Ain Roesley Phenotypes for gene: UNC13A were changed from Congenital myasthenia; dyskinesia; autism; developmental delay to Congenital myasthenia; dyskinesia; autism; developmental delay; neurodevelopmental disorder MONDO#0700092, UNC13A-related
Intellectual disability syndromic and non-syndromic v0.5229 UNC13A Ain Roesley Classified gene: UNC13A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5229 UNC13A Ain Roesley Gene: unc13a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5228 UNC13A Ain Roesley reviewed gene: UNC13A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO#0700092, UNC13A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.885 UNC13A Ain Roesley Phenotypes for gene: UNC13A were changed from Congenital myasthenia; dyskinesia; autism; developmental delay to Congenital myasthenia; dyskinesia; autism; developmental delay; neurodevelopmental disorder MONDO#0700092, UNC13A-related
Mendeliome v1.884 UNC13A Ain Roesley Classified gene: UNC13A as Green List (high evidence)
Mendeliome v1.884 UNC13A Ain Roesley Gene: unc13a has been classified as Green List (High Evidence).
Mendeliome v1.883 UNC13A Ain Roesley reviewed gene: UNC13A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO#0700092, UNC13A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.883 RANBP2 Bryony Thompson Phenotypes for gene: RANBP2 were changed from to familial acute necrotizing encephalopathy MONDO:0011953
Mendeliome v1.882 RANBP2 Bryony Thompson Mode of inheritance for gene: RANBP2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.881 RANBP2 Bryony Thompson Publications for gene: RANBP2 were set to
Craniosynostosis v1.61 CDC45 Yetong Chen reviewed gene: CDC45: Rating: GREEN; Mode of pathogenicity: None; Publications: 33639314, 27884935; Phenotypes: Meier-Gorlin syndrome 7, MIM#617063; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v1.61 MAN2B1 Yetong Chen gene: MAN2B1 was added
gene: MAN2B1 was added to Craniosynostosis. Sources: Expert Review
Mode of inheritance for gene: MAN2B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2B1 were set to 34429528; 33288889; 35242565
Phenotypes for gene: MAN2B1 were set to Mannosidosis, alpha-, types I and II, MIM# 248500
Review for gene: MAN2B1 was set to GREEN
Added comment: A total of 3 unrelated individuals are reported.
PMID 34429528 reports a patient (case 1) with compound heterozygous MAN2B1 variants (c.1830+1G>C and c.2248C>T) who had craniosynostosis.
PMID 33288889 reports a patient with recessive MAN2B1 variants (c.1055 T > C,p.Leu352Pro) who presented craniosynostosis.
PMID 35242565 reports a patient (patient 3) with compound heterozygous MAN2B1 variants (c.2245C > T, p.Arg749Trp and c.2355G > A, p.Thr785*) who had craniosynostosis.
Sources: Expert Review
Craniosynostosis v1.61 IL6ST Yetong Chen gene: IL6ST was added
gene: IL6ST was added to Craniosynostosis. Sources: Expert Review
Mode of inheritance for gene: IL6ST was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL6ST were set to 32566365; 28747427
Phenotypes for gene: IL6ST were set to Hyper-IgE recurrent infection syndrome 4B, autosomal recessive, MIM# 618523
Review for gene: IL6ST was set to AMBER
Added comment: PMID 32566365 describes a patient with homozygous IL6ST variants (p.R281Q) who had craniosynostosis. Abnormalities in nasofrontal sutures and reduced interdigitation of premaxillary sutures were seen in mouse models with homozygous R281Q variants in the IL6ST gene.
PMID 28747427 report a patient with homozygous IL6ST variants (p.N404Y) who had craniosynostosis.
Sources: Expert Review
Craniosynostosis v1.61 FBXO11 Yetong Chen gene: FBXO11 was added
gene: FBXO11 was added to Craniosynostosis. Sources: Expert Review
Mode of inheritance for gene: FBXO11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBXO11 were set to 34429528; 30057029
Phenotypes for gene: FBXO11 were set to intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, MIM# 618089
Review for gene: FBXO11 was set to GREEN
Added comment: A total of 3 unrelated individuals are reported.
PMID 34429528 reports a patient with a de novo FBXO11 variant (c.2731_2732insGACA, p.Thr911Argfs*5) who had craniosynostosis.
PMID 30057029 reports 2 patients (patients 5 and 11) with monoallelic FBXO11 variants (c.2518T>C, p.Ser840Pro and c.1042−1G>C with unknown p.) who had sagittal and metopic craniosynostosis, respectively.
Sources: Expert Review
Motor Neurone Disease v0.138 FIG4 Sangavi Sivagnanasundram reviewed gene: FIG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 19118816, 20301623; Phenotypes: Amyotrophic Lateral Sclerosis Type 11 (MONDO: 0012945, MIM#612577); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.138 DCTN1 Sangavi Sivagnanasundram reviewed gene: DCTN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15326253, 12062019; Phenotypes: {Amyotrophic lateral sclerosis, susceptibility to} - MIM# 105400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.880 GATAD2A Bryony Thompson Publications for gene: GATAD2A were set to https://doi.org/10.1016/j.xhgg.2023.100198; 17565372
Mendeliome v1.879 GATAD2A Bryony Thompson changed review comment from: https://doi.org/10.1016/j.xhgg.2023.100198 - Five unrelated individuals with a neurodevelopmental disorder identified with 3 missense & 2 LoF (4 de novo & 1 unknown inheritance). The shared clinical features with variable expressivity include global developmental delay (4/4), craniofacial dysmorphism (3/5), structural brain defects (2/3), musculoskeletal anomalies (3/5), vision/hearing defects (2/3), gastrointestinal/renal defects (2/3). Loss of function is the expected mechanism of disease. In vitro assays of one of the missense variants (p.Cys420Tyr) demonstrates disruption of GATAD2A integration with CHD3, CHD4, and CHD5
PMID: 17565372 - null mouse model is embryonic lethal.
Sources: Literature; to: PMID: 37181331 - Five unrelated individuals with a neurodevelopmental disorder identified with 3 missense & 2 LoF (4 de novo & 1 unknown inheritance). The shared clinical features with variable expressivity include global developmental delay (4/4), craniofacial dysmorphism (3/5), structural brain defects (2/3), musculoskeletal anomalies (3/5), vision/hearing defects (2/3), gastrointestinal/renal defects (2/3). Loss of function is the expected mechanism of disease. In vitro assays of one of the missense variants (p.Cys420Tyr) demonstrates disruption of GATAD2A integration with CHD3, CHD4, and CHD5
PMID: 17565372 - null mouse model is embryonic lethal.
Sources: Literature
Mendeliome v1.879 GATAD2A Bryony Thompson edited their review of gene: GATAD2A: Changed publications: 37181331, 17565372
Motor Neurone Disease v0.138 ANG Sangavi Sivagnanasundram reviewed gene: ANG: Rating: GREEN; Mode of pathogenicity: None; Publications: 17886298, 16501576, 18087731, 20301623; Phenotypes: Amyotrophic Lateral Sclerosis 9 (MONDO: 0012753, MIM#611895); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.138 ALS2 Sangavi Sivagnanasundram reviewed gene: ALS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24562058, 11586298; Phenotypes: Amyotrophic lateral sclerosis 2, juvenile (MIM# 205100, MONDO: MONDO:0008780); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v1.61 KAT6B Yetong Chen gene: KAT6B was added
gene: KAT6B was added to Craniosynostosis. Sources: Expert Review
Mode of inheritance for gene: KAT6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KAT6B were set to 33288889; 28696035
Phenotypes for gene: KAT6B were set to SBBYSS syndrome, MIM# 603736
Review for gene: KAT6B was set to GREEN
Added comment: Three unrelated patients are reported.
PMID 33288889 reports a patient with a KAT6B variant (c.3769_3772del, p.Lys1258Glyfs*13) who was diagnosed with craniosynostosis.
PMID 28696035 reports 2 patients with different monoallelic KAT6B variants (c.4572dupT, p.Thr1525Tyrfs*16 and c.4205_4206delCT, p.Ser1402Cysfs*5, respectively) who had sagittal craniosynostosis.
Sources: Expert Review
Craniosynostosis v1.61 KAT6A Yetong Chen Deleted their review
Craniosynostosis v1.61 CDK13 Zornitza Stark Marked gene: CDK13 as ready
Craniosynostosis v1.61 CDK13 Zornitza Stark Gene: cdk13 has been classified as Green List (High Evidence).
Craniosynostosis v1.61 CDK13 Zornitza Stark Classified gene: CDK13 as Green List (high evidence)
Craniosynostosis v1.61 CDK13 Zornitza Stark Gene: cdk13 has been classified as Green List (High Evidence).
Craniosynostosis v1.60 ARID1B Zornitza Stark Marked gene: ARID1B as ready
Craniosynostosis v1.60 ARID1B Zornitza Stark Gene: arid1b has been classified as Green List (High Evidence).
Craniosynostosis v1.60 ARID1B Zornitza Stark Classified gene: ARID1B as Green List (high evidence)
Craniosynostosis v1.60 ARID1B Zornitza Stark Gene: arid1b has been classified as Green List (High Evidence).
Craniosynostosis v1.59 NFIX Zornitza Stark Marked gene: NFIX as ready
Craniosynostosis v1.59 NFIX Zornitza Stark Gene: nfix has been classified as Green List (High Evidence).
Craniosynostosis v1.59 NFIX Zornitza Stark Classified gene: NFIX as Green List (high evidence)
Craniosynostosis v1.59 NFIX Zornitza Stark Gene: nfix has been classified as Green List (High Evidence).
Craniosynostosis v1.58 KAT6A Zornitza Stark Publications for gene: KAT6A were set to 30245513; 25728777
Craniosynostosis v1.57 AHDC1 Zornitza Stark Marked gene: AHDC1 as ready
Craniosynostosis v1.57 AHDC1 Zornitza Stark Gene: ahdc1 has been classified as Green List (High Evidence).
Craniosynostosis v1.57 AHDC1 Zornitza Stark Classified gene: AHDC1 as Green List (high evidence)
Craniosynostosis v1.57 AHDC1 Zornitza Stark Gene: ahdc1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.36 ACTB Luisa Weiss changed review comment from: Three independent cases in one cohort study.
Sources: Literature; to: Three independent cases in one cohort study.
Sources: Literature
Cerebral Palsy v1.36 ACTB Luisa Weiss gene: ACTB was added
gene: ACTB was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ACTB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ACTB were set to 33528536
Phenotypes for gene: ACTB were set to Baraitser-Winter syndrome 1 MIM#243310
Review for gene: ACTB was set to GREEN
Added comment: Three independent cases in one cohort study.
Sources: Literature
Cerebral Palsy v1.36 ADCY5 Luisa Mackenroth gene: ADCY5 was added
gene: ADCY5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ADCY5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADCY5 were set to 33528536; 33098801
Phenotypes for gene: ADCY5 were set to Dyskinesia with orofacial involvement MIM#606703
Mode of pathogenicity for gene: ADCY5 was set to Other
Review for gene: ADCY5 was set to GREEN
Added comment: Multiple individuals reported in two different cohort studies analyzing children diagnosed with CP. Clinical overlap with childhood onset dystonia likely. Reported mutations in CP patients indicate gain-of-function mechanism, but loss-of-function mechanism has been described for allelic mutations.
Sources: Literature
Craniosynostosis v1.56 CDK13 Yetong Chen changed review comment from: A total of 4 unrelated individuals are reported.
PMID 34429528 reports a patient with a monoallelic CDK13 variant (c.2563G>C, p.Asp855His) who had metopic synostosis.
PMID 28807008 mentioned 2 patients with craniosynostosis were identified from 9 individuals with CDK13 variants. However, detailed information about the 2 patients is not provided.
PMID 33288889 reported a patient with a CDK13 variant (c.2524 A > G, p.Asn842Asp) who presented with craniosynostosis.
Sources: Expert Review; to: A total of 4 unrelated individuals are reported.
PMID 34429528 reports a patient with a monoallelic CDK13 variant (c.2563G>C, p.Asp855His) who had metopic synostosis.
PMID 28807008 mentions 2 patients with craniosynostosis were identified from 9 individuals with CDK13 variants. However, detailed information about the 2 patients is not provided.
PMID 33288889 reports a patient with a CDK13 variant (c.2524 A > G, p.Asn842Asp) who presented with craniosynostosis.
Sources: Expert Review
Craniosynostosis v1.56 CDK13 Yetong Chen gene: CDK13 was added
gene: CDK13 was added to Craniosynostosis. Sources: Expert Review
Mode of inheritance for gene: CDK13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDK13 were set to 34429528; 28807008; 33288889
Phenotypes for gene: CDK13 were set to Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder, MIM# 617360
Review for gene: CDK13 was set to GREEN
Added comment: A total of 4 unrelated individuals are reported.
PMID 34429528 reports a patient with a monoallelic CDK13 variant (c.2563G>C, p.Asp855His) who had metopic synostosis.
PMID 28807008 mentioned 2 patients with craniosynostosis were identified from 9 individuals with CDK13 variants. However, detailed information about the 2 patients is not provided.
PMID 33288889 reported a patient with a CDK13 variant (c.2524 A > G, p.Asn842Asp) who presented with craniosynostosis.
Sources: Expert Review
Craniosynostosis v1.56 ARID1B Yetong Chen gene: ARID1B was added
gene: ARID1B was added to Craniosynostosis. Sources: Expert Review
Mode of inheritance for gene: ARID1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARID1B were set to 36118902; 34429528; 27474218; 32530565
Phenotypes for gene: ARID1B were set to Coffin-Siris syndrome 1, MIM# 135900
Review for gene: ARID1B was set to GREEN
Added comment: A total of 4 unrelated individuals are reported.
PMID 36118902 reports a patient with an ARID1B variant (chr6:g.157431670_157431676 delCCAGTCA) who presented with sagittal craniosynostosis.
PMID 34429528 identifies a patient (case 16) with an ARID1B variant (c.3594delinsCCCCCA) by screening 127 families classified with craniosynostosis.
PMID 27474218 reported a patient (patient 10) with an ARID1B variant (c.1468_1472delTGGGC) who presented with craniosynostosis.
PMID 32530565 listed a patient (OKI-047-1 M) harbouring an ARID1B variant (c.2277delC) who had trigonocephaly.
Sources: Expert Review
Craniosynostosis v1.56 NFIX Yetong Chen gene: NFIX was added
gene: NFIX was added to Craniosynostosis. Sources: Expert Review
Mode of inheritance for gene: NFIX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFIX were set to 33288889; 35997807
Phenotypes for gene: NFIX were set to Malan syndrome, MIM# 614753
Review for gene: NFIX was set to GREEN
Added comment: PMID 33288889 reports a patient with an NFIX variant (c.143 T > A, p.Met48Lys) who presented craniosynostosis.
PMID 35997807: Of 25 patients with lambdoid craniosynostosis, 4 unrelated patients carried NFIX variants. The patient with the c.143 T > A (p.Met48Lys) variant of the NFIX gene has been reported by PMID 33288889.
Sources: Expert Review
Craniosynostosis v1.56 KAT6A Yetong Chen reviewed gene: KAT6A: Rating: GREEN; Mode of pathogenicity: None; Publications: 33288889, 28696035; Phenotypes: SBBYSS syndrome, MIM# 603736; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mosaic skin disorders v1.10 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease; Tasmanian Clinical Genetics Service
Pulmonary Fibrosis_Interstitial Lung Disease v0.54 NAF1 Zornitza Stark Phenotypes for gene: NAF1 were changed from Pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148 to Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7, MIM# 620365
Pulmonary Fibrosis_Interstitial Lung Disease v0.53 NAF1 Zornitza Stark reviewed gene: NAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7, MIM# 620365; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.879 NAF1 Zornitza Stark Phenotypes for gene: NAF1 were changed from Pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148 to Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7, MIM# 620365
Mendeliome v1.878 NAF1 Zornitza Stark reviewed gene: NAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7, MIM# 620365; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bone Marrow Failure v1.41 NAF1 Zornitza Stark Phenotypes for gene: NAF1 were changed from Pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148 to Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7, MIM# 620365
Bone Marrow Failure v1.40 NAF1 Zornitza Stark reviewed gene: NAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7, MIM# 620365; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Muscular dystrophy and myopathy_Paediatric v0.146 RYR1 Bryony Thompson Classified gene: RYR1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.146 RYR1 Bryony Thompson Gene: ryr1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.145 RYR1 Bryony Thompson edited their review of gene: RYR1: Added comment: Congenital myopathy is reported in both dominant and recessive forms. Loss of function is the disease mechanism for recessive RYR1-related myopathy, whereas gain-of-function is typically the mechanism for dominant disease.; Changed publications: 22473935, 30611313, 8220422, 12112081; Changed phenotypes: RYR1-related myopathy MONDO:0100150; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.878 ZNF292 Michelle Torres reviewed gene: ZNF292: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal dominant 64, MIM#619188; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5228 ZNF292 Michelle Torres reviewed gene: ZNF292: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal dominant 64, MIM#619188; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.107 ESAM Zornitza Stark Phenotypes for gene: ESAM were changed from Neurodevelopmental disorder (MONDO#0700092), ESAM-related to Neurodevelopmental disorder with intracranial haemorrhage, seizures, and spasticity, MIM# 620371
Fetal anomalies v1.106 ESAM Zornitza Stark reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with intracranial haemorrhage, seizures, and spasticity, MIM# 620371; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5228 ESAM Zornitza Stark Phenotypes for gene: ESAM were changed from Neurodevelopmental disorder (MONDO#0700092), ESAM-related to Neurodevelopmental disorder with intracranial haemorrhage, seizures, and spasticity, MIM# 620371
Intellectual disability syndromic and non-syndromic v0.5227 ESAM Zornitza Stark reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with intracranial haemorrhage, seizures, and spasticity, MIM# 620371; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1849 ESAM Zornitza Stark Phenotypes for gene: ESAM were changed from Neurodevelopmental disorder (MONDO#0700092), ESAM-related to Neurodevelopmental disorder with intracranial haemorrhage, seizures, and spasticity, MIM# 620371
Genetic Epilepsy v0.1848 ESAM Zornitza Stark reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with intracranial haemorrhage, seizures, and spasticity, MIM# 620371; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.878 ESAM Zornitza Stark Phenotypes for gene: ESAM were changed from Neurodevelopmental disorder (MONDO#0700092), ESAM-related to Neurodevelopmental disorder with intracranial haemorrhage, seizures, and spasticity, MIM# 620371
Mendeliome v1.877 ESAM Zornitza Stark reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with intracranial haemorrhage, seizures, and spasticity, MIM# 620371; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.91 ESAM Zornitza Stark Phenotypes for gene: ESAM were changed from Neurodevelopmental disorder (MONDO#0700092), ESAM-related to Neurodevelopmental disorder with intracranial haemorrhage, seizures, and spasticity, MIM# 620371
Brain Calcification v1.90 ESAM Zornitza Stark reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with intracranial haemorrhage, seizures, and spasticity, MIM# 620371; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v1.56 AHDC1 Yetong Chen gene: AHDC1 was added
gene: AHDC1 was added to Craniosynostosis. Sources: Expert Review
Mode of inheritance for gene: AHDC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AHDC1 were set to 27884935; 30858058; 30152016; 27148574; 33288889
Phenotypes for gene: AHDC1 were set to Xia-Gibbs syndrome, MIM# 615829
Review for gene: AHDC1 was set to GREEN
Added comment: More than 3 unrelated individuals are reported.
PMID 27884935 scanned craniosynostosis patients and identified an AHDC1 variant (c.2373_2374delTG, p.C791fs*57) from a patient with craniosynostosis.
PMID 30858058 reports a patient with a heterozygous AHDC1 variant (c.4370 A>G, p.Asp1457Gly) who had craniosynostosis.
PMID 30152016 reports a patient (patient 1) with a heterozygous AHDC1 variant (c.2473C>T; p.Q825*) who had craniosynostosis.
PMID 27148574 reports a patient (patient 3) with an AHDC1 variant (c.1881delG
p.Q627Hfs*105) who had sagittal craniosynostosis.
PMID 33288889: Of 94 individuals with syndromic craniosynostosis, 2 individuals carried AHDC1 variants (c.3185_3186del p.(Thr1062Serfs*63) and c.2772del p.(Arg925Glufs*7), respectively).
Sources: Expert Review
Brain Calcification v1.90 ZBTB20 Zornitza Stark Marked gene: ZBTB20 as ready
Brain Calcification v1.90 ZBTB20 Zornitza Stark Gene: zbtb20 has been classified as Green List (High Evidence).
Brain Calcification v1.90 ZBTB20 Zornitza Stark Classified gene: ZBTB20 as Green List (high evidence)
Brain Calcification v1.90 ZBTB20 Zornitza Stark Gene: zbtb20 has been classified as Green List (High Evidence).
Brain Calcification v1.89 ZBTB20 Yetong Chen gene: ZBTB20 was added
gene: ZBTB20 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: ZBTB20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB20 were set to 32734340; 25017102
Phenotypes for gene: ZBTB20 were set to Primrose syndrome, MIM# 259050
Review for gene: ZBTB20 was set to GREEN
Added comment: PMID 32266967 reports 4 patients (1, 2, 22 and 24) with different ZBTB20 variants (p.Gln209Arg, p.Cys580Tyr, p.His624Pro, and p.Met625Val) who had brain calcifications.
PMID reports 3 patients (11D5135, 12D6966 and PRS_02) with different ZBTB20 variants (p.T601I, p.G602A and p.V626M) who had intracranial calcification.
Sources: Expert list
Microcephaly v1.204 HPDL Lucy Spencer gene: HPDL was added
gene: HPDL was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPDL were set to 33188300
Phenotypes for gene: HPDL were set to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (MIM#619026)
Review for gene: HPDL was set to GREEN
Added comment: PMID: 33188300 cohort of infantile neurodegenerative condition, all have biallelic HPDL variants. 7 of 14 individuals have microcephaly, however its noted that head circumference was not remarkable at birth but smaller head circumference/microcephaly was seen by 5 years old.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v0.145 CHST14 Bryony Thompson Marked gene: CHST14 as ready
Muscular dystrophy and myopathy_Paediatric v0.145 CHST14 Bryony Thompson Gene: chst14 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.145 CHST14 Bryony Thompson Classified gene: CHST14 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.145 CHST14 Bryony Thompson Gene: chst14 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.144 CHST14 Bryony Thompson gene: CHST14 was added
gene: CHST14 was added to Muscular dystrophy_Paediatric. Sources: Expert list
Mode of inheritance for gene: CHST14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHST14 were set to 26373698; 20842734; 36833362
Phenotypes for gene: CHST14 were set to Ehlers-Danlos syndrome, musculocontractural type 1 MIM# 601776
Review for gene: CHST14 was set to GREEN
gene: CHST14 was marked as current diagnostic
Added comment: Well-established gene-disease association. MC-EDS represents a differential diagnosis within the congenital myopathy spectrum of disease. Myopathy also present in the null mouse model.
Sources: Expert list
Muscular dystrophy and myopathy_Paediatric v0.143 CACNA1S Bryony Thompson Marked gene: CACNA1S as ready
Muscular dystrophy and myopathy_Paediatric v0.143 CACNA1S Bryony Thompson Gene: cacna1s has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.143 CACNA1S Bryony Thompson Classified gene: CACNA1S as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.143 CACNA1S Bryony Thompson Gene: cacna1s has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.142 CACNA1S Bryony Thompson gene: CACNA1S was added
gene: CACNA1S was added to Muscular dystrophy_Paediatric. Sources: Expert list
Mode of inheritance for gene: CACNA1S was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CACNA1S were set to 28012042; 31227654; 33060286
Phenotypes for gene: CACNA1S were set to Congenital myopathy MONDO:0019952
Review for gene: CACNA1S was set to GREEN
gene: CACNA1S was marked as current diagnostic
Added comment: At least 5 families with biallelic variants and 3 families with monoallelic missense variants (mainly de novo) with congenital myopathy. A decrease in protein level and a major impairment of Ca2+ release induced by depolarization in cultured myotubes was identified in both the dominant and recessive families. Thus, loss of function is the mechanism of disease for CACNA1S-related congenital myopathy.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.145 UNC45B Sangavi Sivagnanasundram gene: UNC45B was added
gene: UNC45B was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Other
Mode of inheritance for gene: UNC45B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UNC45B were set to 33217308; 31852522
Phenotypes for gene: UNC45B were set to Myofibrillar myopathy 11 (MIM#619178)
Review for gene: UNC45B was set to GREEN
Added comment: Onset is within the first decade of life typically indicated by slow progression of proximal muscle weakness.

PMID: 33217308; 31852522
11 individuals from 9 unrelated families with symptoms of progressive proximal muscle weakness.

PMID: 31852522
Muscle biopsy was conducted on one individual which showed myopathic changes with core-like structures
Sources: Other
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.145 SVIL Sangavi Sivagnanasundram gene: SVIL was added
gene: SVIL was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Other
Mode of inheritance for gene: SVIL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SVIL were set to 32779703
Phenotypes for gene: SVIL were set to Myofibrillar myopathy 10 (MIM#619040)
Review for gene: SVIL was set to AMBER
Added comment: Onset is typically within the first or second decade of life while some individuals of onset in early childhood.
Typical features at onset is muscle pain, cramping, and exercise fatigue.

PMID: 32779703
2 affected individuals from 2 unrelated consanguineous families with hypertrophic muscles and muscle rigidity
Sources: Other
Mendeliome v1.877 ARFGEF3 Ain Roesley reviewed gene: ARFGEF3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Muscular dystrophy and myopathy_Paediatric v0.141 CFL2 Bryony Thompson Marked gene: CFL2 as ready
Muscular dystrophy and myopathy_Paediatric v0.141 CFL2 Bryony Thompson Gene: cfl2 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.141 CFL2 Bryony Thompson Classified gene: CFL2 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.141 CFL2 Bryony Thompson Gene: cfl2 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.140 CFL2 Bryony Thompson Publications for gene: CFL2 were set to PMID: 17160903; 22560515
Muscular dystrophy and myopathy_Paediatric v0.139 CCDC78 Bryony Thompson Marked gene: CCDC78 as ready
Muscular dystrophy and myopathy_Paediatric v0.139 CCDC78 Bryony Thompson Gene: ccdc78 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.145 MYL2 Sangavi Sivagnanasundram gene: MYL2 was added
gene: MYL2 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Other
Mode of inheritance for gene: MYL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYL2 were set to 23365102; 9673982
Phenotypes for gene: MYL2 were set to Myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy (MIM#619424)
Review for gene: MYL2 was set to GREEN
Added comment: Onset is in the first few weeks of life.
Typical features include hypotrophy of skeletal and cardiac muscle

PMID: 23365102; 9673982
13 affected individuals from 6 unrelated family with progressive muscle weakness and cardiomyopathy
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.139 CCDC78 Bryony Thompson Classified gene: CCDC78 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v0.139 CCDC78 Bryony Thompson Gene: ccdc78 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.138 BIN1 Bryony Thompson Marked gene: BIN1 as ready
Muscular dystrophy and myopathy_Paediatric v0.138 BIN1 Bryony Thompson Gene: bin1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.138 BIN1 Bryony Thompson Publications for gene: BIN1 were set to 17676042; 29950440
Muscular dystrophy and myopathy_Paediatric v0.137 BIN1 Bryony Thompson Classified gene: BIN1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.137 BIN1 Bryony Thompson Added comment: Comment on list classification: ClinGen Definititive for semidominant centronuclear myopathy by the Congenital myopathy GCEP - Classification - 27/04/2020
Muscular dystrophy and myopathy_Paediatric v0.137 BIN1 Bryony Thompson Gene: bin1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.136 ASCC3 Bryony Thompson Marked gene: ASCC3 as ready
Muscular dystrophy and myopathy_Paediatric v0.136 ASCC3 Bryony Thompson Gene: ascc3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.136 ASCC3 Bryony Thompson Classified gene: ASCC3 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.136 ASCC3 Bryony Thompson Gene: ascc3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.135 ASCC1 Bryony Thompson Marked gene: ASCC1 as ready
Muscular dystrophy and myopathy_Paediatric v0.135 ASCC1 Bryony Thompson Gene: ascc1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.135 ASCC1 Bryony Thompson Classified gene: ASCC1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.135 ASCC1 Bryony Thompson Gene: ascc1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.134 DNAJB4 Bryony Thompson Marked gene: DNAJB4 as ready
Muscular dystrophy and myopathy_Paediatric v0.134 DNAJB4 Bryony Thompson Gene: dnajb4 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.134 DNAJB4 Bryony Thompson Classified gene: DNAJB4 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.134 DNAJB4 Bryony Thompson Gene: dnajb4 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.133 DNAJB4 Bryony Thompson reviewed gene: DNAJB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 36264506; Phenotypes: Myopathy, MONDO:0005336, DNAJB4-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.133 ADSSL1 Bryony Thompson Marked gene: ADSSL1 as ready
Muscular dystrophy and myopathy_Paediatric v0.133 ADSSL1 Bryony Thompson Gene: adssl1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.133 ADSSL1 Bryony Thompson Phenotypes for gene: ADSSL1 were changed from Myopathy Distal 5 (MONDO:0014877; MIM#617030) to Nemaline myopathy MONDO:0018958
Muscular dystrophy and myopathy_Paediatric v0.132 ADSSL1 Bryony Thompson Publications for gene: ADSSL1 were set to 32646962
Muscular dystrophy and myopathy_Paediatric v0.131 ADSSL1 Bryony Thompson Publications for gene: ADSSL1 were set to PMID: 3650622; 28268051; 32646962
Muscular dystrophy and myopathy_Paediatric v0.131 ADSSL1 Bryony Thompson Classified gene: ADSSL1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.131 ADSSL1 Bryony Thompson Gene: adssl1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.130 ADSSL1 Bryony Thompson reviewed gene: ADSSL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32646962; Phenotypes: Nemaline myopathy MONDO:0018958; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.130 ACTN2 Bryony Thompson Classified gene: ACTN2 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.130 ACTN2 Bryony Thompson Gene: actn2 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.129 ACTN2 Bryony Thompson Classified gene: ACTN2 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.129 ACTN2 Bryony Thompson Gene: actn2 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.128 ACTN2 Bryony Thompson Marked gene: ACTN2 as ready
Muscular dystrophy and myopathy_Paediatric v0.128 ACTN2 Bryony Thompson Gene: actn2 has been removed from the panel.
Muscular dystrophy and myopathy_Paediatric v0.128 ACTN2 Bryony Thompson reviewed gene: ACTN2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30701273; Phenotypes: Myopathy, congenital with structured cores and Z-line abnormalities MIM#618654; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.145 KY Sangavi Sivagnanasundram gene: KY was added
gene: KY was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Other
Mode of inheritance for gene: KY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KY were set to 27484770; 27485408; 30591934; 11136708
Phenotypes for gene: KY were set to Myopathy, myofibrillar, 7 (MIM#617114)
Review for gene: KY was set to GREEN
Added comment: Onset is early childhood with slow progression of muscle weakness

PMID: 27484770; 27485408; 30591934
4 individuals from 3 unrelated consanguineous families with slowly progressive myopathy.
Muscle biopsy showed myopathic changes (increased variability in fibre size) and all individuals had a homozygous mutation present in the KY gene.

PMID: 11136708
A mouse model showed myopathy degeneration in the presence of a mutation in KY.
Histopathology on the mutant mouse confirmed the importance of KY protein in muscle growth and function.
Sources: Other
Rhabdomyolysis and Metabolic Myopathy v0.168 GFER Sangavi Sivagnanasundram gene: GFER was added
gene: GFER was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Other
Mode of inheritance for gene: GFER was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GFER were set to 28155230; 19409522; 26018198
Phenotypes for gene: GFER were set to Myopathy, mitochondrial progressive, with congenital cataract and developmental delay (MIM#613076)
Review for gene: GFER was set to GREEN
Added comment: Onset - at birth and/or during infancy

8 individuals from 4 unrelated families with clinical symptoms of hypotonia and elevated plasma lactate levels.
Sources: Other
Rhabdomyolysis and Metabolic Myopathy v0.168 FASTKD2 Sangavi Sivagnanasundram gene: FASTKD2 was added
gene: FASTKD2 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Other
Mode of inheritance for gene: FASTKD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FASTKD2 were set to 31944455; 18771761
Phenotypes for gene: FASTKD2 were set to Combined oxidative phosphorylation deficiency 44 (MIM#618855)
Review for gene: FASTKD2 was set to GREEN
Added comment: - Onset in infancy or early childhood
- Features typically include global developmental delay, hypotonia, and abnormal movements.

5 individuals from 4 unrelated families with features of with hypotonia, increased serum lactate and phenotypes relating to hypertrophic cardiomyopathy

PMID: 31944455
Functional study using HEK293 cells showed the depletion in FASTKD2 protein resulting in defective mitochondrial RNA translation.
Sources: Other
Rhabdomyolysis and Metabolic Myopathy v0.168 AIFM1 Sangavi Sivagnanasundram gene: AIFM1 was added
gene: AIFM1 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Other
Mode of inheritance for gene: AIFM1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: AIFM1 were set to 20362274; 22019070; 26173962
Phenotypes for gene: AIFM1 were set to Combined oxidative phosphorylation deficiency 6 (COXPD6) (MIM#300816); Encephalamyopathy, Mitochondrial, X-Linked
Review for gene: AIFM1 was set to GREEN
Added comment: - Onset is in utero or in infancy
- Affected individuals typically present with hypotonia, impaired psychomotoro development with decreased enzymatic activity, specifically in skeletal muscle or fibroblasts

6 individuals from 3 unrelated families presented with hypotonia with muscle weakness and increased plasma lactate and a hemizygous mutation in AIFM1 causative of Combined oxidative phosphorylation deficiency 6 (COXPD6).

PMID: 20362274
2 individuals (first cousins) from one family with Hypotonia and hypo-areflexia and increased lactate in plasma and both individuals carried a hemizygous deletion
In vitro studies showed that in the presence of the deletion, the inner mitochondrial membrane is destabilised causing damage to the respiratory chain structure and activities.

PMID: 22019070
2 brothers (one deceased) with hyptonia and symptoms of hypertrophic cardiomyopathy (HCM) and complete cytochrome C oxidase deficiency on a histochemistry staining.

PMID: 26173962
2 individuals from one family (cousins) with hemizyggous mutation in AIFM1
Both presented with hypotonia with muscle weakness and increased plasma lactate
Segregation study showed unaffected mother was a carrier for the hemizygous mutation
Sources: Other
Brain Calcification v1.89 XPR1 Zornitza Stark Publications for gene: XPR1 were set to 25938945
Brain Calcification v1.88 WDR45 Zornitza Stark Classified gene: WDR45 as Amber List (moderate evidence)
Brain Calcification v1.88 WDR45 Zornitza Stark Gene: wdr45 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.87 VARS2 Zornitza Stark Marked gene: VARS2 as ready
Brain Calcification v1.87 VARS2 Zornitza Stark Gene: vars2 has been classified as Red List (Low Evidence).
Brain Calcification v1.87 VARS2 Zornitza Stark Classified gene: VARS2 as Red List (low evidence)
Brain Calcification v1.87 VARS2 Zornitza Stark Gene: vars2 has been classified as Red List (Low Evidence).
Brain Calcification v1.86 TYROBP Zornitza Stark Publications for gene: TYROBP were set to 30242731
Brain Calcification v1.85 TSC2 Zornitza Stark Publications for gene: TSC2 were set to
Brain Calcification v1.84 TBCE Zornitza Stark Marked gene: TBCE as ready
Brain Calcification v1.84 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Brain Calcification v1.84 TBCE Zornitza Stark Classified gene: TBCE as Green List (high evidence)
Brain Calcification v1.84 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Brain Calcification v1.83 TBCE Zornitza Stark reviewed gene: TBCE: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypoparathyroidism-retardation-dysmorphism syndrome, MIM# 241410; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.83 XPR1 Yetong Chen reviewed gene: XPR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27230854, 29955172, 33433330; Phenotypes: Basal ganglia calcification, idiopathic, 6, MIM# 616413; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rhabdomyolysis and Metabolic Myopathy v0.168 AGK Sangavi Sivagnanasundram gene: AGK was added
gene: AGK was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Other
Mode of inheritance for gene: AGK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGK were set to 22284826
Phenotypes for gene: AGK were set to Sengers Syndrome (MIM#212350; MONDO:0008922)
Review for gene: AGK was set to GREEN
Added comment: Mitochondrial disorder with typical features such as hypertrophic cardiomyopathy, skeletal myopathy and lactic acidosis

PMID: 22284826
Predicted LoF variants in 10 individuals from unrelated families
> 5 individuals with confirmed combined respiratory-chain-complex deficiency in muscle tissue as well as lactic acidosis.
Sources: Other
Rhabdomyolysis and Metabolic Myopathy v0.168 AARS2 Sangavi Sivagnanasundram gene: AARS2 was added
gene: AARS2 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Other
Mode of inheritance for gene: AARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AARS2 were set to 21549344; 25058219
Phenotypes for gene: AARS2 were set to Combined oxidative phosphorylation deficiency 8 MIM#614096
Review for gene: AARS2 was set to GREEN
Added comment: PMID: 21549344
2 Individuals with infantile mitochondrial HCM and lactic acidosis as well as a severe COX deficiency

PMID: 25058219
5 individuals from unrelated families with a mutation in AARS and phenotypic features of cardiomyopathy but only 3 individuals presented with lactic acidosis.
Sources: Other
Cardiomyopathy_Paediatric v0.160 RRAGC Zornitza Stark Phenotypes for gene: RRAGC were changed from Pediatric Dilated Cardiomyopathy to Dilated cardiomyopathy (MONDO:0005021), RRAGC-related
Cardiomyopathy_Paediatric v0.159 RRAGC Zornitza Stark Publications for gene: RRAGC were set to PMID: 29367541; 27234373
Cardiomyopathy_Paediatric v0.158 RRAGC Zornitza Stark Classified gene: RRAGC as Green List (high evidence)
Cardiomyopathy_Paediatric v0.158 RRAGC Zornitza Stark Gene: rragc has been classified as Green List (High Evidence).
Mendeliome v1.877 RRAGC Zornitza Stark Phenotypes for gene: RRAGC were changed from Dilated cardiomyopathy; cataract to Dilated cardiomyopathy (MONDO:0005021), RRAGC-related
Mendeliome v1.876 RRAGC Zornitza Stark Classified gene: RRAGC as Green List (high evidence)
Mendeliome v1.876 RRAGC Zornitza Stark Gene: rragc has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.128 TPM3 Sangavi Sivagnanasundram edited their review of gene: TPM3: Changed mode of pathogenicity: Other
Muscular dystrophy and myopathy_Paediatric v0.128 TRIP4 Sangavi Sivagnanasundram gene: TRIP4 was added
gene: TRIP4 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: TRIP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIP4 were set to 27008887; 31794073
Phenotypes for gene: TRIP4 were set to ?Muscular dystrophy, congenital, Davignon-Chauveau type (MIM#617066)
Review for gene: TRIP4 was set to GREEN
Added comment: PMID: 27008887
4 individuals from a consanguineous French family with congenital muscular dystrophy

PMID: 31794073
5 individuals from unrelated families with phenotypic onset in childhood or at birth consistent with congenital muscular dystrophy.
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 TPM3 Sangavi Sivagnanasundram gene: TPM3 was added
gene: TPM3 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: TPM3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TPM3 were set to 26418456; 18300303; 10619715; 12196661; 18382475
Phenotypes for gene: TPM3 were set to Congenital myopathy 4A, autosomal dominant (MIM#255310); Congenital myopathy 4B, autosomal recessive (MIM#609284)
Review for gene: TPM3 was set to GREEN
Added comment: Variable age of onset due to the variability of phenotypes. Mutations in TPM3 cause a diverse group of congenital myopathies all characterised by muscle weakness/hypotonia.

AD Congenital Myopathy:
PMID: 26418456
Quantitative in vitro motility assay show that gain of function is mechanism of disease - mutations in the TPM3 gene led to an increased function in the myofibres/muscle cells.
2 unrelated individuals with ΔE218 and ΔE224 de novo deletions in TPM3 with muscle stiffness. Both muscle biopsies showed features of mild myopathy.

PMID: 18300303
4 individuals with phenotypic features of congenital myopathy and mutation present in TPM3

AR Congenital myopathy:
PMID: 10619715
Individual from consanguineous parents with severe symptoms of congenital myopathy

PMID: 12196661
Individual who is a compound heterozygote for nemaline myopathy

PMID: 18382475
Affected individuals from two turkish families with myopathy phenotypes.
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 TPM2 Sangavi Sivagnanasundram gene: TPM2 was added
gene: TPM2 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: TPM2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TPM2 were set to 17846275; 23378224
Phenotypes for gene: TPM2 were set to Nemaline myopathy 4, autosomal dominant (MIM#609285)
Review for gene: TPM2 was set to GREEN
Added comment: - Variable age of onset
- Phenotypic symptoms overlap with CAP syndrome

PMID: 17846275
2 individuals identified with mutations in TPM2 however only one had clinical features and a muscle biopsy (with an accumulation of nemaline rods), concordant with nemaline myopathy.

PMID: 23378224
8 individuals from 5 unrelated families
Presence of congenital contractures in early childhood and all had the presence of rods in their muscle biopsies
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 TNNC2 Sangavi Sivagnanasundram gene: TNNC2 was added
gene: TNNC2 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: TNNC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNNC2 were set to 33755597
Phenotypes for gene: TNNC2 were set to Congenital Myopathy 15 (MIM#62016)
Review for gene: TNNC2 was set to AMBER
Added comment: Age of onset is soon after birth

PMID: 33755597
2 individuals from unrelated families
Muscle biopsies showed hypertrophy or slow-twitch myofibres.
Sources: Other
Brain Calcification v1.83 WDR45 Yetong Chen gene: WDR45 was added
gene: WDR45 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: WDR45 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: WDR45 were set to 26859818; 25301227
Phenotypes for gene: WDR45 were set to Neurodegeneration with brain iron accumulation 5, MIM# 300894
Review for gene: WDR45 was set to AMBER
Added comment: PMID 26859818 reports a patient with a heterozygous WDR45 variant (c.400G > A) who had symmetrical calcification of the medial globus pallidi.
PMID 25301227 reports a patient with a heterozygous WDR45 variant (c.488del C p.Pro163Argfs*34) who had bilateral dense calcification of the globus pallidus.
Sources: Expert list
Muscular dystrophy and myopathy_Paediatric v0.128 STAC3 Sangavi Sivagnanasundram gene: STAC3 was added
gene: STAC3 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: STAC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAC3 were set to 28411587; 28777491
Phenotypes for gene: STAC3 were set to Congenital myopathy 13 (MIM#255995)
Review for gene: STAC3 was set to GREEN
Added comment: Also known as Bailey-Bloch congenital myopathy and Native American myopathy (NAM)

PMID: 28411587
An individual with congenital muscle weakness and contracture and clinical phenotypes consistent with myopathy.

PMID: 28777491
3 individuals from 2 unrelated consanguineous families with clinical symptoms of myopathy.

(Note: Individuals with a mutation in STAC3 are shown to have MH susceptibility in the presence of anesthesia.)
Sources: Other
Brain Calcification v1.83 VARS2 Yetong Chen gene: VARS2 was added
gene: VARS2 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: VARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VARS2 were set to 29314548
Phenotypes for gene: VARS2 were set to Combined oxidative phosphorylation deficiency 20, MIM# 615917
Review for gene: VARS2 was set to RED
Added comment: Limited evidence supports the causal role of the VARS2 gene in brain calcification.
PMID 29314548 reports a patient (Patient 5) with compound heterozygous VARS2 variants (c.1135G > A, p.Ala379Thr and c.1877C > A, p.Ala626Asp) who had symmetrical bilateral basal ganglia calcification.
Sources: Expert list
Brain Calcification v1.83 TYROBP Yetong Chen reviewed gene: TYROBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 11402114; Phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1, MIM# 221770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.128 SPEG Sangavi Sivagnanasundram gene: SPEG was added
gene: SPEG was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: SPEG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPEG were set to 25087613; 30412272
Phenotypes for gene: SPEG were set to Centronuclear myopathy 5, MIM# 615959
Review for gene: SPEG was set to GREEN
Added comment: Variable age of onset (typically seen from birth to early childhood)

PMID: 25087613
3 unrelated individuals with myopathic changes in their biopsy findings (increased centralize nuclei) and decreased amounts of SPEG protein.

Mouse model showed the increase in centralised nuclei in muscle biopsies concordant with a clinical diagnosis of centronuclear myopathy.

PMID: 30412272
2 individuals from unrelated families with hypotonia at birth as well as other phenotypes concordant with a clinical diagnosis of centronuclear myopathy.
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 PAX7 Sangavi Sivagnanasundram gene: PAX7 was added
gene: PAX7 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: PAX7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAX7 were set to 31092906
Phenotypes for gene: PAX7 were set to Congenital myopathy 19 (MIM#618578)
Review for gene: PAX7 was set to GREEN
Added comment: Infantile onset of progressive muscle weakness and atrophy

PMID: 31092906
5 individuals from 4 unrelated families with consanguineous parents - all having clinical signs of myopathy from birth.
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 MYOD1 Sangavi Sivagnanasundram gene: MYOD1 was added
gene: MYOD1 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: MYOD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYOD1 were set to 26733463; 31260566; 30403323
Phenotypes for gene: MYOD1 were set to Congenital Myopathy 17 (MIM#618975)
Review for gene: MYOD1 was set to GREEN
Added comment: Onset of condition is typically at birth.

PMID: 26733463
3 siblings from a first degree consanguineous family with myopathy phenotype.

PMID: 31260566
Two siblings from a fourth degree consansanguineous family with poor weight gain and motor delay and muscle biopsy suggestive of myopathy.

PMID: 30403323
Patient with motor delay, hypotonia identified with a homozygous variant in MYOD1 causative of congenital myopathy. The variant was shown to segregate in the family.
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 MYL1 Sangavi Sivagnanasundram gene: MYL1 was added
gene: MYL1 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: MYL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYL1 were set to 30275711
Phenotypes for gene: MYL1 were set to Congenital Myopathy 14 (MIM#618414)
Review for gene: MYL1 was set to AMBER
Added comment: Phenotypic onset is seen typically at birth or in utero during pregnancy.
Skeletal muscle biopsy typically show a variation in fibre size with specific atrophy of the fast-twitch type II fibres.

PMID: 30275711
2 individuals from unrelated consanguineous families.
Zebrafish model showed a reduced muscle development resulting in the aberrant phenotypes.
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 MYBPC1 Sangavi Sivagnanasundram gene: MYBPC1 was added
gene: MYBPC1 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: MYBPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYBPC1 were set to 31264822; 31025394
Phenotypes for gene: MYBPC1 were set to Congenital Myopathy 16 (MIM#618524)
Review for gene: MYBPC1 was set to GREEN
Added comment: age of onset is seen to be typically during infancy

PMID: 31264822
4 individuals from 3 unrelated families with myopathy related phenotypes

PMID: 31025394
2 individuals from unrelated families with myopathy
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 MTMR14 Sangavi Sivagnanasundram gene: MTMR14 was added
gene: MTMR14 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: MTMR14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MTMR14 were set to 20400459; 20817957; 19465920; 17008356
Phenotypes for gene: MTMR14 were set to {Centronuclear myopathy, autosomal, modifier of} (MIM#160150)
Review for gene: MTMR14 was set to AMBER
Added comment: Functional assays show the effect of the protein on the gene function that related to the phenotypes expected, however the gene has only been reported and confirmed to cause myopathy in one case.

PMID: 20400459; 20817957; 19465920
Mouse and Zebrafish models show the effect of loss of function of MTMR14 protein due to mutations in MTMR14 which resulted in phenotypic features of myopathy

PMID: 17008356
Reported in two families with myopathy however the second individual had an alternate diagnosis.
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 MAP3K20 Sangavi Sivagnanasundram gene: MAP3K20 was added
gene: MAP3K20 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: MAP3K20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAP3K20 were set to 27816943
Phenotypes for gene: MAP3K20 were set to Centronuclear myopathy 6 with fiber-type disproportion (MIM#617760; MONDO:0054695)
Review for gene: MAP3K20 was set to GREEN
Added comment: Age of onset - Infancy or early childhood

Phenotype and muscle biopsy abnormalities are variable - centralized nuclei and fibre type disproportion seem to be a common finding

PMID: 27816943
6 individuals from 3 unrelated consanguineous families with myopathy
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 LMOD3 Sangavi Sivagnanasundram gene: LMOD3 was added
gene: LMOD3 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: LMOD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMOD3 were set to 25250574; 28815944; 30291184
Phenotypes for gene: LMOD3 were set to Nemaline myopathy 10 (MIM# 616165; MONDO:0014513)
Review for gene: LMOD3 was set to GREEN
Added comment: Age of onset is typically during pregnancy (antenatal) however severity of the condition is variable.
Typical phenotypes include: severe generalized hypotonia and weakness at birth, respiratory insufficiency, feeding difficulties, and bulbar weakness

PMID: 25250574
Multiple individuals from unrelated families (21 individuals from 14 patients).
Segregation analysis was consistent of an AR inheritance
Zebrafish model showed the complete loss of function in myotubes resulting in abnormal motor function.
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 KLHL41 Sangavi Sivagnanasundram gene: KLHL41 was added
gene: KLHL41 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: KLHL41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KLHL41 were set to 24268659
Phenotypes for gene: KLHL41 were set to Nemaline Myopathy 9 (MIM#615731; MONDO:0014326)
Review for gene: KLHL41 was set to GREEN
Added comment: Age of onset is not definitive - condition has high phenotypic variability

PMID: 24268659
Zebrafish functional study model showed the loss of function of KLHL41 resulting in highly diminished motor function.

5 unrelated children with nemaline myopathy 9. Muscle biopsies in individuals showed the presence of sarcoplamisc rods in myofibers.
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 KLHL40 Sangavi Sivagnanasundram gene: KLHL40 was added
gene: KLHL40 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: KLHL40 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KLHL40 were set to 23746549
Phenotypes for gene: KLHL40 were set to Nemaline myopathy 8, autosomal recessive, MIM# 615348
Review for gene: KLHL40 was set to GREEN
Added comment: PMID: 23746549
Multiple individuals from unrelated families identified with NEM (both severe and milder forms)
Study showed that KLHL40 mutations are more likely to cause severe NEM

Identified founder mutation, c.1582G>A, in Japanese population. Was also found in Kurdish and Turkish population.
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 KBTBD13 Sangavi Sivagnanasundram gene: KBTBD13 was added
gene: KBTBD13 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: KBTBD13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KBTBD13 were set to 21104864; 11731279; 21109227
Phenotypes for gene: KBTBD13 were set to Nemaline myopathy 6, autosomal dominant (MIM# 609273; MONDO:0012237)
Review for gene: KBTBD13 was set to GREEN
Added comment: PMID: 21104864; 11731279; 21109227
4 individuals from unrelated families with clinical features consistent with nemaline myopathy

(articles reference the gene NEM6 - previous name)
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 HRAS Sangavi Sivagnanasundram gene: HRAS was added
gene: HRAS was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: HRAS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HRAS were set to 17412879
Phenotypes for gene: HRAS were set to Congenital myopathy with excess of muscle spindles (MIM#218040)
Review for gene: HRAS was set to AMBER
Added comment: A variant of Costello Syndrome which is typically characterised by diffuse hypotonia, short stature, developmental delay etc.

Age of onset - birth to early childhood

Most of the mutations related to CMEMS are inherited in an Autosomal Dominant manner, some can be caused by Somatic mutations as well.

PMID: 17412879
4 unrelated individuals identified with a mutation in HRAS and clinical features causative of congenital myopathy with excess of muscle spindles (CMEMS). No functional evidence or animal model study conducted yet
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 HACD1 Sangavi Sivagnanasundram gene: HACD1 was added
gene: HACD1 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: HACD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HACD1 were set to 32426512; 27939133; 33354762; 23933735
Phenotypes for gene: HACD1 were set to Congenital myopathy 11 (MIM#619967; MONDO:0019952)
Review for gene: HACD1 was set to GREEN
Added comment: Age of onset - from birth to early childhood (typically) but is not progressive

PMID: 32426512; 27939133
Individual from consanguineous parents present with a LINE insertation mutation in HACD1 known to cause a form of centronuclear myopathy in dogs.
Developed myopathy features from the age of 4

PMID: 33354762
3 individuals from unrelated families with a homozygous mutation causative of congenital myopathy. Age of onset of symptoms varied between birth to early childhood in these patients. The symptoms showed that the disorder is not progressive and muscle weakness improves in late childhood.

PMID: 23933735
Large consanguineous family with 4 carrying a homozygous mutation in HACD1 causative of congenital myopathy.
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 FXR1 Sangavi Sivagnanasundram gene: FXR1 was added
gene: FXR1 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: FXR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FXR1 were set to 30770808; 35393337
Phenotypes for gene: FXR1 were set to Congenital myopathy 9B, proximal, with minicore lesions (MIM#618823; MONDO:0032937)
Review for gene: FXR1 was set to GREEN
Added comment: Variable age of onset - typically early to late childhood

PMID: 30770808
4 individuals from 2 unrelated families (3 individuals reported from the same family) present with phenotypic features of myopathy such as hypotonia.

PMID: 35393337
8 individuals from 4 unrelated families identified with bi-allelic variants with myopathy phenotypes
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 EPG5 Sangavi Sivagnanasundram gene: EPG5 was added
gene: EPG5 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: EPG5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EPG5 were set to 23222957
Phenotypes for gene: EPG5 were set to Vici Syndrome (MONDO: 0009452; MIM#242840)
Review for gene: EPG5 was set to GREEN
Added comment: Rare congenital disorder (that is reported in multiple individuals) - individuals typically present with profound psychomotor retardation and hypotonia due to myopathy.

Age of onset is typically early childhood.

PMID: 23222957
>6 individuals from unrelated families identified with mutations in EPG5 and phenotypic features related to Vici Syndrome
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 DYNC1H1 Sangavi Sivagnanasundram gene: DYNC1H1 was added
gene: DYNC1H1 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: DYNC1H1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DYNC1H1 were set to PMID: 2245967; 25609763
Phenotypes for gene: DYNC1H1 were set to Spinal muscular atrophy, lower extremity-predominant 1, (MIM#158600; MONDO:0008026)
Review for gene: DYNC1H1 was set to GREEN
Added comment: Phenotypes can resemble those similar to congenital myopathy
Age of onset ranges from birth to early childhood

PMID: 22459677
Phenotypes included early childood onset of proximal leg weakness with muscle atropy and significant motor delay

PMID: 25609763
>10 individuals with SMA phenotypic features similar to congenital myopathy
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 DHX16 Sangavi Sivagnanasundram gene: DHX16 was added
gene: DHX16 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: DHX16 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DHX16 were set to 36211162
Phenotypes for gene: DHX16 were set to Neuromuscular disease and ocular or auditory anomalies with or without seizures (MIM#618733; MONDO:0032890)
Review for gene: DHX16 was set to RED
Added comment: Gene not related to congenital myopathies but has phenotype overlap

PMID: 36211162
One individual presents with severe hypotonia as well as sensorineural deafness and a mixed axonal sensory with developmental delay.
Identified a de novo vairant present causative of Neuromuscular disease and ocular or auditory anomalies with or without seizures.
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 CNTN1 Sangavi Sivagnanasundram gene: CNTN1 was added
gene: CNTN1 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: CNTN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNTN1 were set to 10926398
Phenotypes for gene: CNTN1 were set to Congenital Myopathy 12, Compton-North myopathy (MONDO:0012929; MIM#612540)
Review for gene: CNTN1 was set to AMBER
Added comment: PMID: 10926398
single family reported with clinical features consistent with severe lethal myopathy
(age of onset is unknown as only one family has been reported)
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 CFL2 Sangavi Sivagnanasundram gene: CFL2 was added
gene: CFL2 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: CFL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFL2 were set to PMID: 17160903; 22560515
Phenotypes for gene: CFL2 were set to Nemaline myopathy 7 (MONDO:0012538; MIM#610687)
Review for gene: CFL2 was set to GREEN
Added comment: PMID: 17160903; 22560515
Age of onset - from birth to early childhood (typically around the ages of expected childhood milestones)
- 4 individuals from 2 unrelated consangineous families with clinical phenotypes consistent with congenital myopathy
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 CCDC78 Sangavi Sivagnanasundram gene: CCDC78 was added
gene: CCDC78 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: CCDC78 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCDC78 were set to 22818856
Phenotypes for gene: CCDC78 were set to Centronuclear Myopathy (MIM#614807; MONDO: 0018947)
Review for gene: CCDC78 was set to AMBER
Added comment: PMID: 22818856
5 individuals in the same family with features of myopathy
(Hypotonia, excessive fatigue, prominent myalgias)
Mutations in this gene are not common for congenital myopathy.
Sources: Other
Brain Calcification v1.83 TSC2 Yetong Chen reviewed gene: TSC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21175459, 30628968, 19258292, 28786492; Phenotypes: Tuberous sclerosis-2, MIM# 613254; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Muscular dystrophy and myopathy_Paediatric v0.128 ASCC3 Sangavi Sivagnanasundram gene: ASCC3 was added
gene: ASCC3 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: ASCC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASCC3 were set to 35047834
Phenotypes for gene: ASCC3 were set to Congenital Myopathy (MONDO:0019952); Neuromuscular Symptoms
Review for gene: ASCC3 was set to GREEN
Added comment: PMID: 35047834
11 individuals from 7 unrelated families present with clinical phenotypes consistent with ASCC3-related myopathy.
All individuals reported developmental delay and muscle weakness but age of onset is unknown
Sources: Other
Muscular dystrophy and myopathy_Paediatric v0.128 ASCC1 Sangavi Sivagnanasundram gene: ASCC1 was added
gene: ASCC1 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: ASCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASCC1 were set to (PMID: 30327447; 35838082; 26924529)
Phenotypes for gene: ASCC1 were set to Congenital Myopathy - MONDO:0019952
Review for gene: ASCC1 was set to GREEN
Added comment: PMID: 30327447; 35838082
>3 individuals from unrelated families with clinical features consistent with congenital myopathy

PMID: 35838082
Individual with congenital myopathy phenotype and a mutation in ASCC1.

PMID: 26924529
Animal study showed the effect on ASCC1 protein function in muscle cells.
Sources: Other
Brain Calcification v1.83 TBCE Yetong Chen gene: TBCE was added
gene: TBCE was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBCE were set to 28138323; 35935360
Phenotypes for gene: TBCE were set to Hypoparathyroidism-retardation-dysmorphism syndrome, MIM# 241410
Review for gene: TBCE was set to AMBER
Added comment: PMID 35935360 reports a total of 63 patients with hypoparathyroidism-retardation-dysmorphism (HRD) Syndrome, of which 32 had brain calcifications. Although the paper states that 25 of 63 patients had genetic diagnoses, the number of patients with brain calcification carrying TBCE variants is unclear.
Sources: Expert list
Mendeliome v1.875 RECQL4 Zornitza Stark Phenotypes for gene: RECQL4 were changed from Baller-Gerold syndrome, MIM# 218600; RAPADILINO syndrome, MIM# 266280; Rothmund-Thomson syndrome, type 2,MIM# 268400 to Baller-Gerold syndrome, MIM# 218600; RAPADILINO syndrome, MIM# 266280; Rothmund-Thomson syndrome, type 2,MIM# 268400; RECON progeroid syndrome, MIM# 620370
Mendeliome v1.874 RECQL4 Zornitza Stark Publications for gene: RECQL4 were set to
Chromosome Breakage Disorders v1.19 RECQL4 Zornitza Stark changed review comment from: Two families reported with a progeroid disorder, however all individuals had the same homozygous missense variant, suggestive of founder effect.; to: PMID 35025765: Two families reported with a progeroid disorder, however all individuals had the same homozygous missense variant, suggestive of founder effect.
Mendeliome v1.873 RECQL4 Zornitza Stark reviewed gene: RECQL4: Rating: RED; Mode of pathogenicity: None; Publications: 35025765; Phenotypes: RECON progeroid syndrome, MIM# 620370; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Chromosome Breakage Disorders v1.19 RECQL4 Zornitza Stark Phenotypes for gene: RECQL4 were changed from Rothmund-Thomson syndrome, type 2, MIM# 268400; RAPADILINO syndrome, MIM# 266280; Baller-Gerold syndrome, MIM# 218600 to Rothmund-Thomson syndrome, type 2, MIM# 268400; RAPADILINO syndrome, MIM# 266280; Baller-Gerold syndrome, MIM# 218600; RECON progeroid syndrome, MIM# 620370
Chromosome Breakage Disorders v1.18 RECQL4 Zornitza Stark Publications for gene: RECQL4 were set to 10319867; 12952869; 15964893
Chromosome Breakage Disorders v1.17 RECQL4 Zornitza Stark edited their review of gene: RECQL4: Added comment: Two families reported with a progeroid disorder, however all individuals had the same homozygous missense variant, suggestive of founder effect.; Changed publications: 10319867, 12952869, 15964893, 35025765
Chromosome Breakage Disorders v1.17 RECQL4 Zornitza Stark edited their review of gene: RECQL4: Changed phenotypes: Rothmund-Thomson syndrome, type 2, MIM# 268400, RAPADILINO syndrome, MIM# 266280, Baller-Gerold syndrome, MIM# 218600, RECON progeroid syndrome, MIM# 620370
Mitochondrial disease v0.868 ATP5O Zornitza Stark Marked gene: ATP5O as ready
Mitochondrial disease v0.868 ATP5O Zornitza Stark Gene: atp5o has been classified as Green List (High Evidence).
Mitochondrial disease v0.868 ATP5O Zornitza Stark Classified gene: ATP5O as Green List (high evidence)
Mitochondrial disease v0.868 ATP5O Zornitza Stark Gene: atp5o has been classified as Green List (High Evidence).
Mitochondrial disease v0.867 ATP5O Zornitza Stark gene: ATP5O was added
gene: ATP5O was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: ATP5O was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5O were set to 34954817; 35621276
Phenotypes for gene: ATP5O were set to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7, MIM# 620359
Review for gene: ATP5O was set to GREEN
Added comment: 4 individuals from three unrelated families reported. Onset in infancy. Features included intrauterine growth retardation, hypotonia, neonatal respiratory distress, and global developmental delay, seizures.
Sources: Literature
Mendeliome v1.873 ATP5O Zornitza Stark Phenotypes for gene: ATP5O were changed from mitochondrial disease, ATP5F1E-related MONDO:0044970 to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7, MIM# 620359
Mendeliome v1.872 ATP5O Zornitza Stark Publications for gene: ATP5O were set to 34954817
Mendeliome v1.871 ATP5O Zornitza Stark Classified gene: ATP5O as Green List (high evidence)
Mendeliome v1.871 ATP5O Zornitza Stark Gene: atp5o has been classified as Green List (High Evidence).
Mendeliome v1.870 ATP5O Zornitza Stark reviewed gene: ATP5O: Rating: GREEN; Mode of pathogenicity: None; Publications: 35621276; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7, MIM# 620359; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5227 SLITRK2 Zornitza Stark Phenotypes for gene: SLITRK2 were changed from Neurodevelopmental disorder, SLITRK2-related MONDO:0700092 to Intellectual developmental disorder, X-linked 111, MIM# 301107
Intellectual disability syndromic and non-syndromic v0.5226 SLITRK2 Zornitza Stark reviewed gene: SLITRK2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked 111, MIM# 301107; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.1848 SLITRK2 Zornitza Stark Phenotypes for gene: SLITRK2 were changed from Neurodevelopmental disorder, SLITRK2-related MONDO:0700092 to Intellectual developmental disorder, X-linked 111, MIM# 301107
Genetic Epilepsy v0.1847 SLITRK2 Zornitza Stark reviewed gene: SLITRK2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked 111, MIM# 301107; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.870 SLITRK2 Zornitza Stark Phenotypes for gene: SLITRK2 were changed from Neurodevelopmental disorder, SLITRK2-related MONDO:0700092 to Intellectual developmental disorder, X-linked 111, MIM# 301107
Mendeliome v1.869 SLITRK2 Zornitza Stark reviewed gene: SLITRK2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked 111, MIM# 301107; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.869 AMFR Yetong Chen gene: AMFR was added
gene: AMFR was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AMFR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMFR were set to 37119330
Phenotypes for gene: AMFR were set to Hereditary spastic paraplegia, MONDO:0019064
Review for gene: AMFR was set to GREEN
Added comment: PMID 37119330 reports 20 individuals harbouring AMFR variants from 8 unrelated, consanguineous families. All patients had early disease onset (<3 years), including motor delay, lower limb hyperreflexia and spastic paraplegia that match the typical phenotypes of hereditary spastic paraplegia.
Sources: Literature
Hereditary Spastic Paraplegia - paediatric v1.61 AMFR Yetong Chen gene: AMFR was added
gene: AMFR was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: AMFR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMFR were set to 37119330
Phenotypes for gene: AMFR were set to Hereditary spastic paraplegia, MONDO:0019064
Review for gene: AMFR was set to GREEN
Added comment: PMID 37119330 reports 20 individuals harbouring AMFR variants from 8 unrelated, consanguineous families. All patients had early disease onset (<3 years), including motor delay, lower limb hyperreflexia and spastic paraplegia that match the typical phenotypes of hereditary spastic paraplegia.
Sources: Literature
Severe Combined Immunodeficiency (absent T present B cells) v1.3 POLD3 Bryony Thompson Marked gene: POLD3 as ready
Severe Combined Immunodeficiency (absent T present B cells) v1.3 POLD3 Bryony Thompson Gene: pold3 has been classified as Amber List (Moderate Evidence).
Severe Combined Immunodeficiency (absent T present B cells) v1.3 POLD3 Bryony Thompson Phenotypes for gene: POLD3 were changed from Severe combined immunodeficiency to Severe combined immunodeficiency MONDO:0015974
Severe Combined Immunodeficiency (absent T present B cells) v1.2 POLD3 Bryony Thompson Publications for gene: POLD3 were set to PMID: 37030525
Severe Combined Immunodeficiency (absent T present B cells) v1.2 POLD3 Bryony Thompson Classified gene: POLD3 as Amber List (moderate evidence)
Severe Combined Immunodeficiency (absent T present B cells) v1.2 POLD3 Bryony Thompson Gene: pold3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.869 POLD3 Bryony Thompson Classified gene: POLD3 as Amber List (moderate evidence)
Mendeliome v1.869 POLD3 Bryony Thompson Gene: pold3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.868 POLD3 Bryony Thompson Marked gene: POLD3 as ready
Mendeliome v1.868 POLD3 Bryony Thompson Gene: pold3 has been classified as Red List (Low Evidence).
Mendeliome v1.868 POLD3 Bryony Thompson gene: POLD3 was added
gene: POLD3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POLD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLD3 were set to 37030525; 36395985; 27524497
Phenotypes for gene: POLD3 were set to Severe combined immunodeficiency MONDO:0015974
Review for gene: POLD3 was set to AMBER
Added comment: Homozygous missense variant (NM_006591.3; p.Ile10Thr) identified in a single Lebanese patient, the product of a consanguineous family, presenting with a syndromic severe combined immunodeficiency with neurodevelopmental delay and hearing loss. POLD3 as well as POLD1 and POLD2 expression was abolished in the patient's cells. Null mouse models are embryonic lethal and demonstrate Pold3 is essential for DNA replication in murine B cells.
Sources: Literature
Osteopetrosis v0.32 SLC4A2 Zornitza Stark Marked gene: SLC4A2 as ready
Osteopetrosis v0.32 SLC4A2 Zornitza Stark Gene: slc4a2 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.128 NEB Sangavi Sivagnanasundram gene: NEB was added
gene: NEB was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: NEB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEB were set to 25205138
Phenotypes for gene: NEB were set to Nemaline Myopathy 2 (MIM#256030; MONDO: 0009725)
Review for gene: NEB was set to GREEN
Added comment: PMID: 25205138
Multiple individuals diagnosed with nemaline myopathy 2 in a well-established gene with variable age of onset
Sources: Other
Combined Immunodeficiency v1.37 POLD2 Bryony Thompson Phenotypes for gene: POLD2 were changed from Low CD4 T cells; Low B cells, normal maturation; recurrent respiratory tract infections, skin infections, warts and molluscum; short stature; intellectual disability to Non-severe combined immunodeficiency due to polymerase delta deficiency MONDO:0800145; Low CD4 T cells; Low B cells, normal maturation; recurrent respiratory tract infections, skin infections, warts and molluscum; short stature; intellectual disability
Combined Immunodeficiency v1.36 POLD2 Bryony Thompson Classified gene: POLD2 as Amber List (moderate evidence)
Combined Immunodeficiency v1.36 POLD2 Bryony Thompson Gene: pold2 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.35 POLD2 Bryony Thompson Publications for gene: POLD2 were set to 31449058
Combined Immunodeficiency v1.35 POLD2 Bryony Thompson Classified gene: POLD2 as Amber List (moderate evidence)
Combined Immunodeficiency v1.35 POLD2 Bryony Thompson Gene: pold2 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.34 POLD2 Bryony Thompson reviewed gene: POLD2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31449058, 36528861; Phenotypes: Non-severe combined immunodeficiency due to polymerase delta deficiency MONDO:0800145; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.867 POLD2 Bryony Thompson edited their review of gene: POLD2: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.867 POLD2 Bryony Thompson Phenotypes for gene: POLD2 were changed from Intellectual disability; immunodeficiency to Non-severe combined immunodeficiency due to polymerase delta deficiency MONDO:0800145
Mendeliome v1.866 POLD2 Bryony Thompson Publications for gene: POLD2 were set to 31449058
Muscular dystrophy and myopathy_Paediatric v0.128 MYPN Sangavi Sivagnanasundram gene: MYPN was added
gene: MYPN was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: MYPN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYPN were set to 28017374
Phenotypes for gene: MYPN were set to Nemaline Myopathy (MIM#617336; MONDO:0018958)
Review for gene: MYPN was set to GREEN
Added comment: PMID: 28017374
Slowly progressive myopathy with onset in childhood
Identified in at least 4 individuals
Sources: Other
Mendeliome v1.865 POLD2 Bryony Thompson Classified gene: POLD2 as Amber List (moderate evidence)
Mendeliome v1.865 POLD2 Bryony Thompson Gene: pold2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.864 POLD2 Bryony Thompson reviewed gene: POLD2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31449058, 36528861; Phenotypes: Non-severe combined immunodeficiency due to polymerase delta deficiency MONDO:0800145; Mode of inheritance: None
Mendeliome v1.864 SLC4A2 Zornitza Stark Marked gene: SLC4A2 as ready
Mendeliome v1.864 SLC4A2 Zornitza Stark Gene: slc4a2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.864 SLC4A2 Zornitza Stark Classified gene: SLC4A2 as Amber List (moderate evidence)
Mendeliome v1.864 SLC4A2 Zornitza Stark Gene: slc4a2 has been classified as Amber List (Moderate Evidence).
Osteopetrosis v0.32 SLC4A2 Zornitza Stark Classified gene: SLC4A2 as Amber List (moderate evidence)
Osteopetrosis v0.32 SLC4A2 Zornitza Stark Gene: slc4a2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.863 SLC4A2 Zornitza Stark gene: SLC4A2 was added
gene: SLC4A2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC4A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A2 were set to 34668226; 20507629
Phenotypes for gene: SLC4A2 were set to Osteopetrosis, autosomal recessive 9, MIM# 620366
Review for gene: SLC4A2 was set to AMBER
Added comment: Single individual reported with homozygous missense variant. However, cattle and mouse models support gene-disease association.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v0.128 DNM2 Sangavi Sivagnanasundram gene: DNM2 was added
gene: DNM2 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: DNM2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DNM2 were set to 17932957; 19122038
Phenotypes for gene: DNM2 were set to Centronuclear Myopathy 1 (MIM#160150; MONDO:0008048)
Review for gene: DNM2 was set to GREEN
Added comment: PMID: 17932957, 19122038
Multiple individuals with centronuclear myopathy.
Age of onset is variable but typically in the early childhood.
Sources: Other
Osteopetrosis v0.31 SLC4A2 Zornitza Stark gene: SLC4A2 was added
gene: SLC4A2 was added to Osteopetrosis. Sources: Literature
Mode of inheritance for gene: SLC4A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A2 were set to 34668226; 20507629
Phenotypes for gene: SLC4A2 were set to Osteopetrosis, autosomal recessive 9, MIM# 620366
Review for gene: SLC4A2 was set to AMBER
Added comment: Single individual reported with homozygous missense variant. However, cattle and mouse models support gene-disease association.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v0.128 DNAJB4 Sangavi Sivagnanasundram gene: DNAJB4 was added
gene: DNAJB4 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: DNAJB4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJB4 were set to 36264506
Phenotypes for gene: DNAJB4 were set to Congenital Myopathy 21 with early respiratory failure (MIM#620326; MONDO:005336)
Review for gene: DNAJB4 was set to GREEN
Added comment: PMID: 36264506
4 individuals from unrelated families with congenital myopathy with variable age of onset
Sources: Other
Disorders of immune dysregulation v0.172 DOCK2 Bryony Thompson Marked gene: DOCK2 as ready
Disorders of immune dysregulation v0.172 DOCK2 Bryony Thompson Gene: dock2 has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.100 C17orf62 Bryony Thompson Marked gene: C17orf62 as ready
Inflammatory bowel disease v0.100 C17orf62 Bryony Thompson Gene: c17orf62 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.172 DOCK2 Bryony Thompson Phenotypes for gene: DOCK2 were changed from HLH to Genetic hemophagocytic lymphohistiocytosis MONDO:0015541
Disorders of immune dysregulation v0.171 DOCK2 Bryony Thompson Classified gene: DOCK2 as Amber List (moderate evidence)
Disorders of immune dysregulation v0.171 DOCK2 Bryony Thompson Gene: dock2 has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.100 C17orf62 Bryony Thompson Classified gene: C17orf62 as Amber List (moderate evidence)
Inflammatory bowel disease v0.100 C17orf62 Bryony Thompson Gene: c17orf62 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.128 BIN1 Sangavi Sivagnanasundram gene: BIN1 was added
gene: BIN1 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: BIN1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: BIN1 were set to 17676042; 29950440
Phenotypes for gene: BIN1 were set to Centronuclear myopathy 2 (MONDO: 0009709; MIM#255200)
Review for gene: BIN1 was set to GREEN
Added comment: PMID: 17676042
3 unrelated consanguineous families with centronuclear myopathy 2.
Age of onset ranged from birth to childhood

PMID: 29950440
Homozygous patients have a more specific and severe phenotype compared to compound heterozygous patients with similar age of onset
Sources: Other
Bone Marrow Failure v1.40 ZCCHC8 Bryony Thompson Marked gene: ZCCHC8 as ready
Bone Marrow Failure v1.40 ZCCHC8 Bryony Thompson Gene: zcchc8 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.40 ZCCHC8 Bryony Thompson Classified gene: ZCCHC8 as Amber List (moderate evidence)
Bone Marrow Failure v1.40 ZCCHC8 Bryony Thompson Gene: zcchc8 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.39 ZCCHC8 Bryony Thompson gene: ZCCHC8 was added
gene: ZCCHC8 was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: ZCCHC8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZCCHC8 were set to 31488579
Phenotypes for gene: ZCCHC8 were set to Pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148
Review for gene: ZCCHC8 was set to AMBER
Added comment: A missense variant (P186L) segregates over 3 generations in a single family, and supporting in vitro assays and mouse model.
Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v0.53 ZCCHC8 Bryony Thompson Phenotypes for gene: ZCCHC8 were changed from Pulmonary fibrosis to Pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148
Pulmonary Fibrosis_Interstitial Lung Disease v0.52 ZCCHC8 Bryony Thompson edited their review of gene: ZCCHC8: Changed phenotypes: Pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148
Mendeliome v1.862 ZCCHC8 Bryony Thompson Phenotypes for gene: ZCCHC8 were changed from Pulmonary fibrosis to pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148
Mendeliome v1.861 ZCCHC8 Bryony Thompson edited their review of gene: ZCCHC8: Changed phenotypes: pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148
Bone Marrow Failure v1.38 NOP10 Bryony Thompson Classified gene: NOP10 as Amber List (moderate evidence)
Bone Marrow Failure v1.38 NOP10 Bryony Thompson Gene: nop10 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.37 NOP10 Bryony Thompson reviewed gene: NOP10: Rating: AMBER; Mode of pathogenicity: None; Publications: 17507419, 32554502; Phenotypes: Dyskeratosis congenita, autosomal recessive 1, MIM#224230, Telomere syndrome MONDO:0100137; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.861 NOP10 Bryony Thompson Phenotypes for gene: NOP10 were changed from Dyskeratosis congenita, autosomal recessive 1, MIM#224230 to Dyskeratosis congenita, autosomal recessive 1, MIM#224230; Telomere syndrome MONDO:0100137
Mendeliome v1.860 NOP10 Bryony Thompson Publications for gene: NOP10 were set to 17507419
Mendeliome v1.859 NOP10 Bryony Thompson Classified gene: NOP10 as Amber List (moderate evidence)
Mendeliome v1.859 NOP10 Bryony Thompson Gene: nop10 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.858 NOP10 Bryony Thompson reviewed gene: NOP10: Rating: AMBER; Mode of pathogenicity: None; Publications: 17507419, 32554502; Phenotypes: Telomere syndrome MONDO:0100137; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pulmonary Fibrosis_Interstitial Lung Disease v0.52 ACD Bryony Thompson Marked gene: ACD as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.52 ACD Bryony Thompson Gene: acd has been classified as Amber List (Moderate Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.52 ACD Bryony Thompson Classified gene: ACD as Amber List (moderate evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.52 ACD Bryony Thompson Gene: acd has been classified as Amber List (Moderate Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.51 ACD Bryony Thompson gene: ACD was added
gene: ACD was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: ACD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACD were set to 31515401; 27807141; 25205116
Phenotypes for gene: ACD were set to pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148
Mode of pathogenicity for gene: ACD was set to Other
Review for gene: ACD was set to AMBER
Added comment: 3 probands reported with heterozygous variants (only 2 of the variants including p.Lys170 look to possibly relevant)
PMID: 31515401 - proband 1 with bone marrow failure and pulmonary fibrosis in the context of a telomere syndrome heterozygous for recurrent p.Lys170del. Proband 2 with idiopathic pulmonary fibrosis heterozygous for p.Lys170Glu. Proband 3 with idiopathic pulmonary fibrosis heterozygous for p.Ala72Glu (9 hets in gnomAD - VUS), which was also found in the unaffected 83 yo father. All patients had a leukocyte telomere length <1st percentiles for age.
PMID: 27807141 - in vitro functional assays suggesting that the recurrent variant p.Lys170del is sufficient to cause the cellular underpinnings of dyskeratosis congenita, acting in a dosage-dependent mechanism rather than dominant-negative.
PMID: 25205116 - Lys170del identified in 18-yo proband, mother, and maternal grandmother presented with bone marrow failure of varying severity, and decreasing ages of presentation in successive generations. All with short telomeres. In vitro assays demonstrate the variant localises to telomeres but fails to recruit telomerase to telomeres.
Sources: Literature
Bone Marrow Failure v1.37 ACD Bryony Thompson Phenotypes for gene: ACD were changed from Dyskeratosis congenita, MIM# 616553 to telomere syndrome MONDO:0100137; dyskeratosis congenita, autosomal dominant 6 MONDO:0014690; Hoyeraal-Hreidarsson syndrome MONDO:0018045
Bone Marrow Failure v1.36 ACD Bryony Thompson Publications for gene: ACD were set to 25205116; 25233904
Bone Marrow Failure v1.35 ACD Bryony Thompson Classified gene: ACD as Green List (high evidence)
Bone Marrow Failure v1.35 ACD Bryony Thompson Gene: acd has been classified as Green List (High Evidence).
Bone Marrow Failure v1.34 ACD Bryony Thompson reviewed gene: ACD: Rating: GREEN; Mode of pathogenicity: None; Publications: 27807141, 31515401, 30995915, 27528712, 25205116, 24316971, 30064976, 33446513, 25233904; Phenotypes: telomere syndrome MONDO:0100137, dyskeratosis congenita, autosomal dominant 6 MONDO:0014690, Hoyeraal-Hreidarsson syndrome MONDO:0018045; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.858 ACD Bryony Thompson Phenotypes for gene: ACD were changed from Dyskeratosis congenita, MIM# 616553 to telomere syndrome MONDO:0100137; dyskeratosis congenita, autosomal dominant 6 MONDO:0014690; Hoyeraal-Hreidarsson syndrome MONDO:0018045
Mendeliome v1.857 ACD Bryony Thompson Publications for gene: ACD were set to 25205116; 25233904
Mendeliome v1.856 ACD Bryony Thompson Classified gene: ACD as Green List (high evidence)
Mendeliome v1.856 ACD Bryony Thompson Gene: acd has been classified as Green List (High Evidence).
Mendeliome v1.855 ACD Bryony Thompson reviewed gene: ACD: Rating: GREEN; Mode of pathogenicity: None; Publications: 27807141, 31515401, 30995915, 27528712, 25205116, 24316971, 30064976, 33446513, 25233904; Phenotypes: telomere syndrome MONDO:0100137, dyskeratosis congenita, autosomal dominant 6 MONDO:0014690, Hoyeraal-Hreidarsson syndrome MONDO:0018045; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.128 ADSSL1 Sangavi Sivagnanasundram gene: ADSSL1 was added
gene: ADSSL1 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: ADSSL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADSSL1 were set to PMID: 3650622; 28268051; 32646962
Phenotypes for gene: ADSSL1 were set to Myopathy Distal 5 (MONDO:0014877; MIM#617030)
Review for gene: ADSSL1 was set to GREEN
Added comment: PMID: 3650622; 28268051
Age of onset 13-17 years in multiple individuals of unrelated families

PMID: 32646962 - Multiple individuals diagnosed with distal myopathy 5 (MD5)
Sources: Other
Brain Calcification v1.83 MT-ATP6 Zornitza Stark Marked gene: MT-ATP6 as ready
Brain Calcification v1.83 MT-ATP6 Zornitza Stark Gene: mt-atp6 has been classified as Red List (Low Evidence).
Brain Calcification v1.83 MT-ATP6 Zornitza Stark Phenotypes for gene: MT-ATP6 were changed from Leigh syndrome, MIM# 256000 to Leigh syndrome, MONDO:0009723
Brain Calcification v1.82 MT-ATP6 Zornitza Stark Classified gene: MT-ATP6 as Red List (low evidence)
Brain Calcification v1.82 MT-ATP6 Zornitza Stark Gene: mt-atp6 has been classified as Red List (Low Evidence).
Brain Calcification v1.81 MT-ATP6 Zornitza Stark reviewed gene: MT-ATP6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Leigh syndrome, MONDO:0009723; Mode of inheritance: MITOCHONDRIAL
Brain Calcification v1.81 GNAS Zornitza Stark Marked gene: GNAS as ready
Brain Calcification v1.81 GNAS Zornitza Stark Gene: gnas has been classified as Green List (High Evidence).
Brain Calcification v1.81 GNAS Zornitza Stark Classified gene: GNAS as Green List (high evidence)
Brain Calcification v1.81 GNAS Zornitza Stark Gene: gnas has been classified as Green List (High Evidence).
Brain Calcification v1.80 MOCS1 Zornitza Stark Marked gene: MOCS1 as ready
Brain Calcification v1.80 MOCS1 Zornitza Stark Gene: mocs1 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.80 MOCS1 Zornitza Stark Classified gene: MOCS1 as Amber List (moderate evidence)
Brain Calcification v1.80 MOCS1 Zornitza Stark Gene: mocs1 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.79 MOCS1 Zornitza Stark reviewed gene: MOCS1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Molybdenum cofactor deficiency A, MIM# 252150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.79 ISG15 Zornitza Stark Marked gene: ISG15 as ready
Brain Calcification v1.79 ISG15 Zornitza Stark Gene: isg15 has been classified as Green List (High Evidence).
Brain Calcification v1.79 ISG15 Zornitza Stark Classified gene: ISG15 as Green List (high evidence)
Brain Calcification v1.79 ISG15 Zornitza Stark Gene: isg15 has been classified as Green List (High Evidence).
Brain Calcification v1.78 PLXNA1 Zornitza Stark Marked gene: PLXNA1 as ready
Brain Calcification v1.78 PLXNA1 Zornitza Stark Gene: plxna1 has been classified as Red List (Low Evidence).
Brain Calcification v1.78 PLXNA1 Zornitza Stark Classified gene: PLXNA1 as Red List (low evidence)
Brain Calcification v1.78 PLXNA1 Zornitza Stark Gene: plxna1 has been classified as Red List (Low Evidence).
Brain Calcification v1.77 TRPM6 Zornitza Stark Marked gene: TRPM6 as ready
Brain Calcification v1.77 TRPM6 Zornitza Stark Gene: trpm6 has been classified as Red List (Low Evidence).
Brain Calcification v1.77 TRPM6 Zornitza Stark Classified gene: TRPM6 as Red List (low evidence)
Brain Calcification v1.77 TRPM6 Zornitza Stark Gene: trpm6 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.128 ACTN2 Sangavi Sivagnanasundram gene: ACTN2 was added
gene: ACTN2 was added to Muscular dystrophy_Paediatric. Sources: Other
Mode of inheritance for gene: ACTN2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ACTN2 were set to 30701273
Phenotypes for gene: ACTN2 were set to Congenital Myopathy 8 (MIM#618654; MONDO: 0032852)
Penetrance for gene: ACTN2 were set to unknown
Review for gene: ACTN2 was set to GREEN
Added comment: PMID: 30701273
2 unrelated individuals with congenital myopathy plus an in vivo zebrafish model showed a loss in protein function resulting in zebrafish embryo hatching defect and impaired motor function.
- Age of onset in both individuals was in the first decade of life
Sources: Other
Mendeliome v1.855 RRAGC Naomi Baker reviewed gene: RRAGC: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:37057673, 27234373, 33057194; Phenotypes: Dilated cardiomyopathy (MONDO:0005021), RRAGC-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v0.157 RRAGC Naomi Baker reviewed gene: RRAGC: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:37057673, 27234373, 33057194; Phenotypes: Dilated cardiomyopathy (MONDO:0005021), RRAGC-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5226 INTS11 Zornitza Stark Phenotypes for gene: INTS11 were changed from Global developmental delay; launguage delay; intellectual disability; impaired motor development; brain atrophy to intellectual disability, MONDO:0001071
Mendeliome v1.855 MCAT Zornitza Stark reviewed gene: MCAT: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Leber hereditary optic neuropathy, autosomal recessive, MONDO:0030309; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.855 MCAT Zornitza Stark Phenotypes for gene: MCAT were changed from progressive autosomal recessive optic neuropathy to Leber hereditary optic neuropathy, autosomal recessive, MONDO:0030309
Mendeliome v1.854 DNAH7 Zornitza Stark Phenotypes for gene: DNAH7 were changed from non-syndromic male infertility due to sperm motility disorder (MONDO#0017173), DNAH7-related to Primary ciliary dyskinesia, MONDO:0016575, DNAH7-related
Mendeliome v1.853 DNAH7 Zornitza Stark reviewed gene: DNAH7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary ciliary dyskinesia, MONDO:0016575, DNAH7-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v1.30 DNAH7 Zornitza Stark Phenotypes for gene: DNAH7 were changed from non-syndromic male infertility due to sperm motility disorder (MONDO#0017173), DNAH7-related to Primary ciliary dyskinesia, MONDO:0016575, DNAH7-related
Mendeliome v1.853 RARA Zornitza Stark commented on gene: RARA: PMID: 37086723 identified a recurrent, heterozygous de novo missense variant in the RARA gene - c.865G>A; (p.Gly289Arg) - in two unrelated individuals. The variant is absent from gnomAD, highly conserved, major grantham score (125) and is located in the hormone receptor domain (DECIPHER).

Both individuals had severe craniosynostosis (sagittal or bicoronal).

Other shared phenotypic features included:
- Limb anomalies (rocker-bottom feet, bowing of the legs, and short upper/lower limbs)
- Additional craniofacial manifestations(microtia, conductive hearing loss, ankyloglossia, esotropia, hypoplastic
nasal bones, and oligodontia)
- Other additional anomalies included renal dysplasia with cysts, tracheomalacia, pulmonary arterial hypertension, developmental delays, hypotonia, cryptorchidism, seizures and adrenal insufficiency.

The authors postulate a gain of function mechanism. No functional studies provided. The gene encodes the retinoic acid receptor. Overlapping phenotypic features in these 2 affected individuals with retinoic acid embryopathy noted by the authors.
Ciliary Dyskinesia v1.29 DNAH7 Zornitza Stark reviewed gene: DNAH7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary ciliary dyskinesia, MONDO:0016575, DNAH7-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic Atrophy v1.17 NDUFA12 Suliman Khan changed review comment from: 9 individual form 6 unrelated families presented with movement disorder phenotypes (dystonia and/or spasticity) to isolated optic atrophy. Basal ganglia abnormalities were observed in 6 patients, two patients had optic atrophy, and one was unremarkable. All patients carried homozygous truncating variants in the NDUFA12 gene PMID: 35141356.
Sources: Literature; to: 9 individuals form 6 unrelated families presented with movement disorder phenotypes (dystonia and/or spasticity) to isolated optic atrophy. Basal ganglia abnormalities were observed in 6 patients, two patients had optic atrophy, and one was unremarkable. All patients carried homozygous truncating variants in the NDUFA12 gene PMID: 35141356.
Sources: Literature
Mendeliome v1.853 RARA Zornitza Stark Phenotypes for gene: RARA were changed from Syndromic chorioretinal coloboma to Craniosynostosis - MONDO:0015469; Syndromic chorioretinal coloboma
Mendeliome v1.852 RARA Zornitza Stark Publications for gene: RARA were set to 31343737
Mendeliome v1.851 RARA Zornitza Stark Classified gene: RARA as Amber List (moderate evidence)
Mendeliome v1.851 RARA Zornitza Stark Gene: rara has been classified as Amber List (Moderate Evidence).
Mendeliome v1.850 RARA Zornitza Stark edited their review of gene: RARA: Added comment: PMID: 37086723 identified a recurrent, heterozygous de novo missense variant in the RARA gene - c.865G>A; (p.Gly289Arg) - in two unrelated individuals. The variant is absent from gnomAD, highly conserved, major grantham score (125) and is located in the hormone receptor domain (DECIPHER).

Both individuals had severe craniosynostosis (sagittal or bicoronal).

Other shared phenotypic features included:
- Limb anomalies (rocker-bottom feet, bowing of the legs, and short upper/lower limbs)
- Additional craniofacial manifestations(microtia, conductive hearing loss, ankyloglossia, esotropia, hypoplastic
nasal bones, and oligodontia)
- Other additional anomalies included renal dysplasia with cysts, tracheomalacia, pulmonary arterial hypertension, developmental delays, hypotonia, cryptorchidism, seizures and adrenal insufficiency.

The authors postulate a gain of function mechanism. No functional studies provided. The gene encodes the retinoic acid receptor. Overlapping phenotypic features in these 2 affected individuals with retinoic acid embryopathy noted by the authors.; Changed rating: AMBER; Changed publications: 31343737, 37086723; Changed phenotypes: Craniosynostosis - MONDO:0015469, Syndromic chorioretinal coloboma; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic Atrophy v1.17 NDUFA12 Zornitza Stark Marked gene: NDUFA12 as ready
Optic Atrophy v1.17 NDUFA12 Zornitza Stark Gene: ndufa12 has been classified as Green List (High Evidence).
Optic Atrophy v1.17 NDUFA12 Zornitza Stark Classified gene: NDUFA12 as Green List (high evidence)
Optic Atrophy v1.17 NDUFA12 Zornitza Stark Gene: ndufa12 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.78 PMEPA1 Zornitza Stark Marked gene: PMEPA1 as ready
Aortopathy_Connective Tissue Disorders v1.78 PMEPA1 Zornitza Stark Gene: pmepa1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.78 PMEPA1 Zornitza Stark Classified gene: PMEPA1 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v1.78 PMEPA1 Zornitza Stark Gene: pmepa1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.77 PMEPA1 Zornitza Stark gene: PMEPA1 was added
gene: PMEPA1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: PMEPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PMEPA1 were set to 36928819
Phenotypes for gene: PMEPA1 were set to Hereditary disorder of connective tissue, MONDO:0023603, PMEPA1-related
Mode of pathogenicity for gene: PMEPA1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: PMEPA1 was set to AMBER
Added comment: PMID: 36928819; Greene, D. et al. (2023) Nat Med. 29(3):679-688.
A paper by Genomics England Research Consortium. Genetic association analysis of 77,539 genomes .

Eight families with truncating variants affecting the same stretch of cytosines in this gene.

In the 100KGP discovery cohort, in three families with Familial thoracic aortic aneurysm disease (FTAAD) of European ancestry, the variant found was an insertion of a cytosine within a seven-cytosine stretch in the last exon, predicted to cause p.(S209Qfs*3). This variant was also identified independently in eight affected members of three pedigrees of Japanese ancestry in a separate Japanese patient group.
(Note: the variant is present in gnomAD v2.1.1 in 22 heterozygotes as a filtered out variant.).

Also, this study found a deletion of one of those cytosines causing p.(S209Afs*61), in one individual or family.
Also, there was one family in Belgium in which the affected members carried a 5-bp deletion in the same stretch of polycytosines inducing a frameshift p.(P207Qfs*3).

Phenotypic analysis of the individuals suggest that the phenotype of these FTAAD individuals and families is more like Loeys-Dietz syndrome.
Sources: Literature
Mendeliome v1.850 PMEPA1 Zornitza Stark Phenotypes for gene: PMEPA1 were changed from Familial thoracic aortic aneurysm disease (FTAAD); Loeys-Dietz syndrome to Hereditary disorder of connective tissue, MONDO:0023603, PMEPA1-related
Mendeliome v1.849 PMEPA1 Zornitza Stark reviewed gene: PMEPA1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Hereditary disorder of connective tissue, MONDO:0023603, PMEPA1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bone Marrow Failure v1.34 NAF1 Bryony Thompson Marked gene: NAF1 as ready
Bone Marrow Failure v1.34 NAF1 Bryony Thompson Gene: naf1 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.34 NAF1 Bryony Thompson Classified gene: NAF1 as Green List (high evidence)
Bone Marrow Failure v1.34 NAF1 Bryony Thompson Added comment: Comment on list classification: Included because of the increased risk for progressive bone marrow failure associated with telomere biology disorders
Bone Marrow Failure v1.34 NAF1 Bryony Thompson Gene: naf1 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.50 NAF1 Bryony Thompson Marked gene: NAF1 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.50 NAF1 Bryony Thompson Gene: naf1 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.50 NAF1 Bryony Thompson Classified gene: NAF1 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.50 NAF1 Bryony Thompson Gene: naf1 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.49 NAF1 Bryony Thompson gene: NAF1 was added
gene: NAF1 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: NAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NAF1 were set to 27510903
Phenotypes for gene: NAF1 were set to Pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148
Review for gene: NAF1 was set to GREEN
Added comment: At least 3 probands/families with telomere-related pulmonary fibrosis and a supporting mouse model
PMID: 27510903 - 5 individuals from 2 unrelated families with pulmonary fibrosis-emphysema and extrapulmonary manifestations including myelodysplastic syndrome and liver disease, with LoF variants. Truncated NAF1 was detected in cells derived from patients, and, in cells in which a frameshift mutation was introduced by genome editing telomerase RNA levels were reduced. Shortened telomere length also segregated with the variants. A Naf1+/- mouse model had reduced telomerase RNA levels

ClinVar - 1 nonsense and 2 splice site variants (ID: 2443185, 1338525, 2443184) called LP by the Genetic Services Laboratory, University of Chicago but no clinical details were provided
- SCV002547372.1 - Garcia Pulmonary Genetics Research Laboratory, Columbia University Irving Medical Center - at least one individual with pulmonary fibrosis and leukocyte telomere length (by qPCR) less than 10th percentile age-adjusted
Sources: Literature
Bone Marrow Failure v1.33 NAF1 Bryony Thompson gene: NAF1 was added
gene: NAF1 was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: NAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NAF1 were set to 27510903
Phenotypes for gene: NAF1 were set to Pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148
Review for gene: NAF1 was set to GREEN
Added comment: At least 3 probands/families with telomere-related pulmonary fibrosis and a supporting mouse model
PMID: 27510903 - 5 individuals from 2 unrelated families with pulmonary fibrosis-emphysema and extrapulmonary manifestations including myelodysplastic syndrome and liver disease, with LoF variants. Truncated NAF1 was detected in cells derived from patients, and, in cells in which a frameshift mutation was introduced by genome editing telomerase RNA levels were reduced. Shortened telomere length also segregated with the variants. A Naf1+/- mouse model had reduced telomerase RNA levels

ClinVar - 1 nonsense and 2 splice site variants (ID: 2443185, 1338525, 2443184) called LP by the Genetic Services Laboratory, University of Chicago but no clinical details were provided
- SCV002547372.1 - Garcia Pulmonary Genetics Research Laboratory, Columbia University Irving Medical Center - at least one individual with pulmonary fibrosis and leukocyte telomere length (by qPCR) less than 10th percentile age-adjusted
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5225 LHX2 Zornitza Stark Marked gene: LHX2 as ready
Intellectual disability syndromic and non-syndromic v0.5225 LHX2 Zornitza Stark Gene: lhx2 has been classified as Green List (High Evidence).
Mendeliome v1.849 NAF1 Bryony Thompson Marked gene: NAF1 as ready
Mendeliome v1.849 NAF1 Bryony Thompson Gene: naf1 has been classified as Green List (High Evidence).
Mendeliome v1.849 NAF1 Bryony Thompson Classified gene: NAF1 as Green List (high evidence)
Mendeliome v1.849 NAF1 Bryony Thompson Gene: naf1 has been classified as Green List (High Evidence).
Mendeliome v1.848 NAF1 Bryony Thompson gene: NAF1 was added
gene: NAF1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NAF1 were set to 27510903
Phenotypes for gene: NAF1 were set to Pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148
Review for gene: NAF1 was set to GREEN
Added comment: At least 3 probands/families with telomere-related pulmonary fibrosis and a supporting mouse model
PMID: 27510903 - 5 individuals from 2 unrelated families with pulmonary fibrosis-emphysema and extrapulmonary manifestations including myelodysplastic syndrome and liver disease, with LoF variants. Truncated NAF1 was detected in cells derived from patients, and, in cells in which a frameshift mutation was introduced by genome editing telomerase RNA levels were reduced. Shortened telomere length also segregated with the variants. A Naf1+/- mouse model had reduced telomerase RNA levels

ClinVar - 1 nonsense and 2 splice site variants (ID: 2443185, 1338525, 2443184) called LP by the Genetic Services Laboratory, University of Chicago but no clinical details were provided
- SCV002547372.1 - Garcia Pulmonary Genetics Research Laboratory, Columbia University Irving Medical Center - at least one individual with pulmonary fibrosis and leukocyte telomere length (by qPCR) less than 10th percentile age-adjusted
Sources: Expert list
Mendeliome v1.847 PMEPA1 Hazel Phillimore changed review comment from: PMID: 36928819; Greene, D. et al. (2023) Nat Med. 29(3):679-688.
A paper by Genomics England Research Consortium. Genetic association analysis of 77,539 genomes .

Eight families with truncating variants affecting the same stretch of cytosines in this gene.

In the 100KGP discovery cohort, in three families with Familial thoracic aortic aneurysm disease (FTAAD) of European ancestry, the variant found was an insertion of a cytosine within a seven-cytosine stretch in the last exon, predicted to cause p.(S209Qfs*3). This variant was also identified independently in eight affected members of three pedigrees of Japanese ancestry in a separate Japanese patient group.
Also, this study found a deletion of one of those cytosines causing p.(S209Afs*61), in one individual or family.
Also, there was one family in Belgium in which the affected members carried a 5-bp deletion in the same stretch of polycytosines inducing a frameshift p.(P207Qfs*3).

Phenotypic analysis of the individuals suggest that the phenotype of these FTAAD individuals and families is more like Loeys-Dietz syndrome.
Sources: Literature; to: PMID: 36928819; Greene, D. et al. (2023) Nat Med. 29(3):679-688.
A paper by Genomics England Research Consortium. Genetic association analysis of 77,539 genomes .

Eight families with truncating variants affecting the same stretch of cytosines in this gene.

In the 100KGP discovery cohort, in three families with Familial thoracic aortic aneurysm disease (FTAAD) of European ancestry, the variant found was an insertion of a cytosine within a seven-cytosine stretch in the last exon, predicted to cause p.(S209Qfs*3). This variant was also identified independently in eight affected members of three pedigrees of Japanese ancestry in a separate Japanese patient group.
(Note: the variant is present in gnomAD v2.1.1 in 22 heterozygotes as a filtered out variant.).

Also, this study found a deletion of one of those cytosines causing p.(S209Afs*61), in one individual or family.
Also, there was one family in Belgium in which the affected members carried a 5-bp deletion in the same stretch of polycytosines inducing a frameshift p.(P207Qfs*3).

Phenotypic analysis of the individuals suggest that the phenotype of these FTAAD individuals and families is more like Loeys-Dietz syndrome.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5225 LHX2 Zornitza Stark Publications for gene: LHX2 were set to PMID:
Intellectual disability syndromic and non-syndromic v0.5224 LHX2 Zornitza Stark Phenotypes for gene: LHX2 were changed from to Neurodevelopmental disorder (MONDO: 0700092)
Intellectual disability syndromic and non-syndromic v0.5223 LHX2 Zornitza Stark Classified gene: LHX2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5223 LHX2 Zornitza Stark Gene: lhx2 has been classified as Green List (High Evidence).
Mendeliome v1.847 PMEPA1 Seb Lunke Marked gene: PMEPA1 as ready
Mendeliome v1.847 PMEPA1 Seb Lunke Gene: pmepa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.847 PMEPA1 Seb Lunke Classified gene: PMEPA1 as Amber List (moderate evidence)
Mendeliome v1.847 PMEPA1 Seb Lunke Gene: pmepa1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.204 LHX2 Zornitza Stark Marked gene: LHX2 as ready
Microcephaly v1.204 LHX2 Zornitza Stark Gene: lhx2 has been classified as Green List (High Evidence).
Microcephaly v1.204 LHX2 Zornitza Stark Classified gene: LHX2 as Green List (high evidence)
Microcephaly v1.204 LHX2 Zornitza Stark Gene: lhx2 has been classified as Green List (High Evidence).
Mendeliome v1.846 LHX2 Zornitza Stark Marked gene: LHX2 as ready
Mendeliome v1.846 LHX2 Zornitza Stark Gene: lhx2 has been classified as Green List (High Evidence).
Mendeliome v1.846 LHX2 Zornitza Stark Classified gene: LHX2 as Green List (high evidence)
Mendeliome v1.846 LHX2 Zornitza Stark Gene: lhx2 has been classified as Green List (High Evidence).
Microcephaly v1.203 LHX2 Manny Jacobs gene: LHX2 was added
gene: LHX2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: LHX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LHX2 were set to PMID: 37057675
Phenotypes for gene: LHX2 were set to Neurodevelopmental disorder (MONDO: 0700092)
Review for gene: LHX2 was set to GREEN
Added comment: PMID: 37057675

Case series of 19 individuals across 18 families.
1 whole gene deletion, 7 missense, 10 predicted LoF variants.
Proposed loss-of-function mechanism.
Variable phenotype, with variable intellectual disability and behavioural (ASD/ADHD) features common.
Microcephaly in 7 individuals.
1 variant inherited from a mildly affected parent, all other variants with parental genotype available shown to be de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5222 CBX1 Zornitza Stark Marked gene: CBX1 as ready
Intellectual disability syndromic and non-syndromic v0.5222 CBX1 Zornitza Stark Gene: cbx1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5222 CNOT9 Zornitza Stark Marked gene: CNOT9 as ready
Intellectual disability syndromic and non-syndromic v0.5222 CNOT9 Zornitza Stark Gene: cnot9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5222 CNOT9 Zornitza Stark Mode of inheritance for gene: CNOT9 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5221 CNOT9 Zornitza Stark Classified gene: CNOT9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5221 CNOT9 Zornitza Stark Gene: cnot9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5220 LHX2 Manny Jacobs reviewed gene: LHX2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37057675; Phenotypes: Neurodevelopmental disorder (MONDO: 0700092); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1847 CNOT9 Zornitza Stark Marked gene: CNOT9 as ready
Genetic Epilepsy v0.1847 CNOT9 Zornitza Stark Gene: cnot9 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1847 CNOT9 Zornitza Stark Mode of inheritance for gene: CNOT9 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1846 CNOT9 Zornitza Stark Classified gene: CNOT9 as Green List (high evidence)
Genetic Epilepsy v0.1846 CNOT9 Zornitza Stark Gene: cnot9 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1846 CNOT9 Zornitza Stark Classified gene: CNOT9 as Green List (high evidence)
Genetic Epilepsy v0.1846 CNOT9 Zornitza Stark Gene: cnot9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5220 CNOT9 Karina Sandoval edited their review of gene: CNOT9: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic Atrophy v1.16 NDUFA12 Suliman Khan changed review comment from: 9 individual form 6 unrelated families presented with movement disorder phenotypes (dystonia and/or spasticity) to isolated optic atrophy. Basal ganglia abnormalities were observed in 6 patients, two patients have optic atrophy, and one was unremarkable. All patients carried homozygous truncating variants in the NDUFA12 gene PMID: 35141356.
Sources: Literature; to: 9 individual form 6 unrelated families presented with movement disorder phenotypes (dystonia and/or spasticity) to isolated optic atrophy. Basal ganglia abnormalities were observed in 6 patients, two patients had optic atrophy, and one was unremarkable. All patients carried homozygous truncating variants in the NDUFA12 gene PMID: 35141356.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5220 CBX1 Seb Lunke Classified gene: CBX1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5220 CBX1 Seb Lunke Gene: cbx1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5219 LHX2 Manny Jacobs gene: LHX2 was added
gene: LHX2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LHX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LHX2 were set to PMID:
Optic Atrophy v1.16 NDUFA12 Suliman Khan gene: NDUFA12 was added
gene: NDUFA12 was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: NDUFA12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA12 were set to PMID: 35141356
Phenotypes for gene: NDUFA12 were set to isolated optic atrophy; MONDO:0003608
Review for gene: NDUFA12 was set to GREEN
Added comment: 9 individual form 6 unrelated families presented with movement disorder phenotypes (dystonia and/or spasticity) to isolated optic atrophy. Basal ganglia abnormalities were observed in 6 patients, two patients have optic atrophy, and one was unremarkable. All patients carried homozygous truncating variants in the NDUFA12 gene PMID: 35141356.
Sources: Literature
Mendeliome v1.845 CNOT9 Karina Sandoval edited their review of gene: CNOT9: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.845 CNOT9 Zornitza Stark Marked gene: CNOT9 as ready
Mendeliome v1.845 CNOT9 Zornitza Stark Gene: cnot9 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1845 CNOT9 Karina Sandoval edited their review of gene: CNOT9: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.845 CBX1 Seb Lunke Marked gene: CBX1 as ready
Mendeliome v1.845 CBX1 Seb Lunke Gene: cbx1 has been classified as Green List (High Evidence).
Craniosynostosis v1.56 RARA Krithika Murali reviewed gene: RARA: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 37086723; Phenotypes: Craniosynostosis - MONDO:0015469; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.845 CNOT9 Zornitza Stark Mode of inheritance for gene: CNOT9 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.844 CBX1 Seb Lunke Classified gene: CBX1 as Green List (high evidence)
Mendeliome v1.844 CBX1 Seb Lunke Gene: cbx1 has been classified as Green List (High Evidence).
Mendeliome v1.843 CNOT9 Zornitza Stark Classified gene: CNOT9 as Green List (high evidence)
Mendeliome v1.843 CNOT9 Zornitza Stark Gene: cnot9 has been classified as Green List (High Evidence).
Craniosynostosis v1.56 RARA Krithika Murali Deleted their review
Mendeliome v1.842 LHX2 Manny Jacobs gene: LHX2 was added
gene: LHX2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LHX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LHX2 were set to PMID: 37057675
Phenotypes for gene: LHX2 were set to Neurodevelopmental disorder (MONDO: 0700092)
Review for gene: LHX2 was set to GREEN
Added comment: PMID: 37057675

Case series of 19 individuals across 18 families.
1 whole gene deletion, 7 missense, 10 predicted LoF variants.
Proposed loss-of-function mechanism.
Variable phenotype, with variable intellectual disability and behavioural (ASD/ADHD) features.
Microcephaly in 7 individuals.
1 variant inherited from a mildly affected parent, all other variants with parental genotype available shown to be de novo.
Sources: Literature
Craniosynostosis v1.56 RARA Krithika Murali reviewed gene: RARA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.842 DNAH7 Seb Lunke Marked gene: DNAH7 as ready
Mendeliome v1.842 DNAH7 Seb Lunke Gene: dnah7 has been classified as Green List (High Evidence).
Mendeliome v1.842 DNAH7 Seb Lunke Classified gene: DNAH7 as Green List (high evidence)
Mendeliome v1.842 DNAH7 Seb Lunke Gene: dnah7 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.157 GPR156 Zornitza Stark Marked gene: GPR156 as ready
Deafness_IsolatedAndComplex v1.157 GPR156 Zornitza Stark Gene: gpr156 has been classified as Green List (High Evidence).
Mendeliome v1.842 MRPL39 Zornitza Stark Phenotypes for gene: MRPL39 were changed from Leigh syndrome MONDO:0009723 to Mitochondrial disease MONDO:0044970
Deafness_IsolatedAndComplex v1.157 GPR156 Zornitza Stark Classified gene: GPR156 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.157 GPR156 Zornitza Stark Gene: gpr156 has been classified as Green List (High Evidence).
Mendeliome v1.841 PMEPA1 Hazel Phillimore gene: PMEPA1 was added
gene: PMEPA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PMEPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PMEPA1 were set to PMID: 36928819
Phenotypes for gene: PMEPA1 were set to Familial thoracic aortic aneurysm disease (FTAAD); Loeys-Dietz syndrome
Mode of pathogenicity for gene: PMEPA1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: PMEPA1 was set to AMBER
Added comment: PMID: 36928819; Greene, D. et al. (2023) Nat Med. 29(3):679-688.
A paper by Genomics England Research Consortium. Genetic association analysis of 77,539 genomes .

Eight families with truncating variants affecting the same stretch of cytosines in this gene.

In the 100KGP discovery cohort, in three families with Familial thoracic aortic aneurysm disease (FTAAD) of European ancestry, the variant found was an insertion of a cytosine within a seven-cytosine stretch in the last exon, predicted to cause p.(S209Qfs*3). This variant was also identified independently in eight affected members of three pedigrees of Japanese ancestry in a separate Japanese patient group.
Also, this study found a deletion of one of those cytosines causing p.(S209Afs*61), in one individual or family.
Also, there was one family in Belgium in which the affected members carried a 5-bp deletion in the same stretch of polycytosines inducing a frameshift p.(P207Qfs*3).

Phenotypic analysis of the individuals suggest that the phenotype of these FTAAD individuals and families is more like Loeys-Dietz syndrome.
Sources: Literature
Ciliary Dyskinesia v1.29 DNAH7 Seb Lunke Marked gene: DNAH7 as ready
Ciliary Dyskinesia v1.29 DNAH7 Seb Lunke Gene: dnah7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5219 INTS11 Seb Lunke Marked gene: INTS11 as ready
Intellectual disability syndromic and non-syndromic v0.5219 INTS11 Seb Lunke Gene: ints11 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v1.29 DNAH7 Seb Lunke Classified gene: DNAH7 as Green List (high evidence)
Ciliary Dyskinesia v1.29 DNAH7 Seb Lunke Gene: dnah7 has been classified as Green List (High Evidence).
Mendeliome v1.841 GPR156 Zornitza Stark Marked gene: GPR156 as ready
Mendeliome v1.841 GPR156 Zornitza Stark Gene: gpr156 has been classified as Green List (High Evidence).
Mendeliome v1.841 GPR156 Zornitza Stark Classified gene: GPR156 as Green List (high evidence)
Mendeliome v1.841 GPR156 Zornitza Stark Gene: gpr156 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1845 CNOT9 Karina Sandoval gene: CNOT9 was added
gene: CNOT9 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CNOT9 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CNOT9 were set to PMID: 37092538
Phenotypes for gene: CNOT9 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: CNOT9 was set to GREEN
Added comment: 7 individuals with de novo variants. In silico predictions of functional relevance. All affected persons have DD/ID, with five of them showing seizures. Other symptoms include.

Symptoms: Neuro dev disorder. ID, Epilepsy. All affected persons have DD/ID, with five of them showing seizures. Other symptoms include muscular hypotonia, facial dysmorphism, and behavioral abnormalities.
Sources: Literature
Deafness_Isolated v1.43 GPR156 Zornitza Stark Marked gene: GPR156 as ready
Deafness_Isolated v1.43 GPR156 Zornitza Stark Gene: gpr156 has been classified as Green List (High Evidence).
Deafness_Isolated v1.43 GPR156 Zornitza Stark Classified gene: GPR156 as Green List (high evidence)
Deafness_Isolated v1.43 GPR156 Zornitza Stark Gene: gpr156 has been classified as Green List (High Evidence).
Mendeliome v1.840 MRPL39 Zornitza Stark Classified gene: MRPL39 as Green List (high evidence)
Mendeliome v1.840 MRPL39 Zornitza Stark Gene: mrpl39 has been classified as Green List (High Evidence).
Craniosynostosis v1.56 RARA Zornitza Stark Marked gene: RARA as ready
Craniosynostosis v1.56 RARA Zornitza Stark Gene: rara has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5219 CNOT9 Karina Sandoval gene: CNOT9 was added
gene: CNOT9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CNOT9 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CNOT9 were set to PMID: 37092538
Phenotypes for gene: CNOT9 were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: CNOT9 was set to GREEN
Added comment: 7 individuals with de novo variants. In silico predictions of functional relevance. All affected persons have DD/ID, with five of them showing seizures. Other symptoms include.

Symptoms: Neuro dev disorder. ID, Epilepsy. All affected persons have DD/ID, with five of them showing seizures. Other symptoms include muscular hypotonia, facial dysmorphism, and behavioral abnormalities.
Sources: Literature
Mendeliome v1.839 CBX1 Daniel Flanagan gene: CBX1 was added
gene: CBX1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CBX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CBX1 were set to PMID: 37087635
Phenotypes for gene: CBX1 were set to Neurodevelopmental disorder (MONDO#0700092), CBX1-related
Review for gene: CBX1 was set to GREEN
Added comment: Three different de novo missense variants identified in three unrelated individuals with developmental delay, hypotonia, autistic features, and variable dysmorphic features such as broad forehead and head circumference above average. Mutant mice displayed increased latency-to-peak response, suggesting the possibility of synaptic delay or myelination deficits. Functional studies confirmed the reduction of mutant HP1β binding to heterochromatin.
Sources: Expert list
Craniosynostosis v1.56 RARA Zornitza Stark Classified gene: RARA as Amber List (moderate evidence)
Craniosynostosis v1.56 RARA Zornitza Stark Gene: rara has been classified as Amber List (Moderate Evidence).
Mendeliome v1.839 MCAT Seb Lunke Classified gene: MCAT as Amber List (moderate evidence)
Mendeliome v1.839 MCAT Seb Lunke Gene: mcat has been classified as Amber List (Moderate Evidence).
Optic Atrophy v1.16 MCAT Seb Lunke Phenotypes for gene: MCAT were changed from Leber hereditary optic neuropathy, autosomal recessive, MONDO:0030309 to Leber hereditary optic neuropathy, autosomal recessive, MONDO:0030309
Mitochondrial disease v0.866 MRPL39 Zornitza Stark Phenotypes for gene: MRPL39 were changed from Mitochondrial disease MONDO:0044970 to Mitochondrial disease MONDO:0044970
Mendeliome v1.838 SRSF1 Zornitza Stark Marked gene: SRSF1 as ready
Mendeliome v1.838 SRSF1 Zornitza Stark Gene: srsf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5219 CBX1 Daniel Flanagan gene: CBX1 was added
gene: CBX1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: CBX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CBX1 were set to PMID: 37087635
Phenotypes for gene: CBX1 were set to Neurodevelopmental disorder (MONDO#0700092), CBX1-related
Review for gene: CBX1 was set to GREEN
Added comment: Three different de novo missense variants identified in three unrelated individuals with developmental delay, hypotonia, autistic features, and variable dysmorphic features such as broad forehead and head circumference above average. Mutant mice displayed increased latency-to-peak response, suggesting the possibility of synaptic delay or myelination deficits. Functional studies confirmed the reduction of mutant HP1β binding to heterochromatin.
Sources: Expert list
Mendeliome v1.838 CNOT9 Karina Sandoval gene: CNOT9 was added
gene: CNOT9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNOT9 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CNOT9 were set to PMID: 37092538
Phenotypes for gene: CNOT9 were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: CNOT9 was set to GREEN
Added comment: 7 individuals with de novo variants. In silico predictions of functional relevance. All affected persons have DD/ID, with five of them showing seizures. Other symptoms include.

Symptoms: Neuro dev disorder. ID, Epilepsy. All affected persons have DD/ID, with five of them showing seizures. Other symptoms include muscular hypotonia, facial dysmorphism, and behavioral abnormalities.
Sources: Literature
Mitochondrial disease v0.866 MRPL39 Zornitza Stark Phenotypes for gene: MRPL39 were changed from Mitochondrial disease MONDO:0044970 to Mitochondrial disease MONDO:0044970
Mitochondrial disease v0.866 MRPL39 Zornitza Stark Marked gene: MRPL39 as ready
Mitochondrial disease v0.866 MRPL39 Zornitza Stark Gene: mrpl39 has been classified as Green List (High Evidence).
Optic Atrophy v1.15 MCAT Seb Lunke Phenotypes for gene: MCAT were changed from progressive autosomal recessive optic neuropathy to Leber hereditary optic neuropathy, autosomal recessive, MONDO:0030309
Mitochondrial disease v0.866 MRPL39 Zornitza Stark Phenotypes for gene: MRPL39 were changed from Leigh Syndrome MONDO:0009723 to Mitochondrial disease MONDO:0044970
Mendeliome v1.838 SRSF1 Zornitza Stark Classified gene: SRSF1 as Green List (high evidence)
Mendeliome v1.838 SRSF1 Zornitza Stark Gene: srsf1 has been classified as Green List (High Evidence).
Craniosynostosis v1.55 RARA Krithika Murali Deleted their review
Mitochondrial disease v0.865 MRPL39 Zornitza Stark Classified gene: MRPL39 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5219 INTS11 Seb Lunke Classified gene: INTS11 as Green List (high evidence)
Mitochondrial disease v0.865 MRPL39 Zornitza Stark Gene: mrpl39 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5219 INTS11 Seb Lunke Gene: ints11 has been classified as Green List (High Evidence).
Optic Atrophy v1.14 MCAT Seb Lunke Classified gene: MCAT as Amber List (moderate evidence)
Optic Atrophy v1.14 MCAT Seb Lunke Gene: mcat has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1845 POLR1A Elena Savva Classified gene: POLR1A as Amber List (moderate evidence)
Genetic Epilepsy v0.1845 POLR1A Elena Savva Gene: polr1a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5218 SRSF1 Zornitza Stark Classified gene: SRSF1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5218 SRSF1 Zornitza Stark Gene: srsf1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.865 MRPL39 Zornitza Stark Classified gene: MRPL39 as Green List (high evidence)
Mitochondrial disease v0.865 MRPL39 Zornitza Stark Gene: mrpl39 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1845 POLR1A Elena Savva Classified gene: POLR1A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5218 INTS11 Seb Lunke Classified gene: INTS11 as Green List (high evidence)
Genetic Epilepsy v0.1845 POLR1A Elena Savva Gene: polr1a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5218 INTS11 Seb Lunke Gene: ints11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5218 SRSF1 Zornitza Stark Marked gene: SRSF1 as ready
Intellectual disability syndromic and non-syndromic v0.5218 SRSF1 Zornitza Stark Gene: srsf1 has been classified as Green List (High Evidence).
Optic Atrophy v1.13 MCAT Seb Lunke Publications for gene: MCAT were set to 31915829
Mitochondrial disease v0.865 MRPL39 Zornitza Stark Classified gene: MRPL39 as Green List (high evidence)
Mitochondrial disease v0.865 MRPL39 Zornitza Stark Gene: mrpl39 has been classified as Green List (High Evidence).
Mendeliome v1.837 DNAH7 Chern Lim gene: DNAH7 was added
gene: DNAH7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAH7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH7 were set to 34476482; 35543642
Phenotypes for gene: DNAH7 were set to non-syndromic male infertility due to sperm motility disorder (MONDO#0017173), DNAH7-related
Review for gene: DNAH7 was set to GREEN
gene: DNAH7 was marked as current diagnostic
Added comment: PMID: 34476482 (Wei et al 2021):
- Hom/chet missense DNAH7 variants in three unrelated infertile patients with idiopathic asthenozoospermia, presented with primary ciliary dyskinesia (PCD)-associated symptoms.
- Functional studies showed expression of DNAH7 in the spermatozoa from the DNAH7-defective patients was significantly decreased.

PMID: 35543642 (Gao et al 2022):
- One proband with idiopathic asthenozoospermia, presented a history of PCD-like symptoms. Hom frameshift variant predicted to cause NMD, both parents are heterozygous.
- Immunofluorescent staining showed DNAH7 signal significantly decreased or was even completely absent in the sperm from the investigated patient.
Sources: Literature
Genetic Epilepsy v0.1845 POLR1A Elena Savva Classified gene: POLR1A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5218 SRSF1 Zornitza Stark Classified gene: SRSF1 as Green List (high evidence)
Genetic Epilepsy v0.1845 POLR1A Elena Savva Gene: polr1a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5218 SRSF1 Zornitza Stark Gene: srsf1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.864 MRPL39 Lilian Downie edited their review of gene: MRPL39: Changed phenotypes: Mitochondrial disease MONDO:0044970
Deafness_IsolatedAndComplex v1.156 GPR156 Anna Ritchie gene: GPR156 was added
gene: GPR156 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: GPR156 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPR156 were set to PMID: 36928819
Phenotypes for gene: GPR156 were set to Sensorineural hearing loss, MONDO:60700002, GPR156-related
Review for gene: GPR156 was set to GREEN
Added comment: Eight affected individuals from three unrelated families all had congenital nonsyndromic bilateral sensorineural hearing loss. Homozygous and compound heterozygous loss of function variants were reported in these families.
Sources: Literature
Deafness_Isolated v1.42 GPR156 Anna Ritchie edited their review of gene: GPR156: Changed rating: GREEN
Ciliary Dyskinesia v1.28 DNAH7 Chern Lim gene: DNAH7 was added
gene: DNAH7 was added to Ciliary Dyskinesia. Sources: Literature
Mode of inheritance for gene: DNAH7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH7 were set to 34476482; 35543642
Phenotypes for gene: DNAH7 were set to non-syndromic male infertility due to sperm motility disorder (MONDO#0017173), DNAH7-related
Review for gene: DNAH7 was set to GREEN
gene: DNAH7 was marked as current diagnostic
Added comment: PMID: 34476482 (Wei et al 2021):
- Hom/chet missense DNAH7 variants in three unrelated infertile patients with idiopathic asthenozoospermia, presented with primary ciliary dyskinesia (PCD)-associated symptoms.
- Functional studies showed expression of DNAH7 in the spermatozoa from the DNAH7-defective patients was significantly decreased.

PMID: 35543642 (Gao et al 2022):
- One proband with idiopathic asthenozoospermia, presented a history of PCD-like symptoms. Hom frameshift variant predicted to cause NMD, both parents are heterozygous.
- Immunofluorescent staining showed DNAH7 signal significantly decreased or was even completely absent in the sperm from the investigated patient.
Sources: Literature
Mendeliome v1.837 MRPL39 Lilian Downie edited their review of gene: MRPL39: Changed rating: GREEN; Changed phenotypes: Mitochondrial disease MONDO:0044970
Genetic Epilepsy v0.1845 POLR1A Elena Savva Classified gene: POLR1A as Amber List (moderate evidence)
Genetic Epilepsy v0.1845 POLR1A Elena Savva Gene: polr1a has been classified as Amber List (Moderate Evidence).
Mendeliome v1.837 INTS11 Seb Lunke Marked gene: INTS11 as ready
Mendeliome v1.837 INTS11 Seb Lunke Gene: ints11 has been classified as Green List (High Evidence).
Mendeliome v1.837 MRPL39 Lilian Downie changed review comment from: AR
3 unrelated individuals, confirmed variants in trans
Functional studies on patient fibroblasts
Multisystem disease, variable onset
2x infants with a clinical diagnosis of Leigh syndrome (congestive cardiac
failure, increased lactates, seizures, apnea, poor feeding, and global developmental delay, leading
to early death (< 1 year of age))
Adult with hypertrophic cardiomyopathy, lactic acidosis, ADHD
Sources: Literature; to: AR
3 unrelated individuals, confirmed variants in trans
Functional studies on patient fibroblasts
Multisystem disease, variable onset
2x infants with a clinical diagnosis of Leigh syndrome (congestive cardiac
failure, increased lactates, seizures, apnea, poor feeding, and global developmental delay, leading
to early death (< 1 year of age))
Adult with hypertrophic cardiomyopathy, lactic acidosis, ADHD
Sources: Literature
Deafness_Isolated v1.42 GPR156 Anna Ritchie gene: GPR156 was added
gene: GPR156 was added to Deafness_Isolated. Sources: Literature
Mode of inheritance for gene: GPR156 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPR156 were set to PMID: 36928819
Phenotypes for gene: GPR156 were set to Sensorineural hearing loss, MONDO:60700002, GPR156-related
Added comment: Eight affected individuals from three unrelated families all had congenital nonsyndromic bilateral sensorineural hearing loss. Homozygous and compound heterozygous loss of function variants were reported in these families.
Sources: Literature
Genetic Epilepsy v0.1844 POLR1A Elena Savva Marked gene: POLR1A as ready
Genetic Epilepsy v0.1844 POLR1A Elena Savva Gene: polr1a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5217 POLR1A Elena Savva Classified gene: POLR1A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5217 POLR1A Elena Savva Gene: polr1a has been classified as Green List (High Evidence).
Mendeliome v1.837 INTS11 Seb Lunke Phenotypes for gene: INTS11 were changed from to intellectual disability, MONDO:0001071
Mendeliome v1.836 INTS11 Melanie Marty changed review comment from: PMID: 37054711 - 15 individuals from 10 unrelated families with bi-allelic variants in INTS11 with global developmental and language delay, intellectual disability, impaired motor development, and brain atrophy.; to: PMID: 37054711 - 15 individuals from 10 unrelated families with bi-allelic variants in INTS11 with global developmental and language delay, intellectual disability, impaired motor development, and brain atrophy.

Functional studies in Drosophila showed that dIntS11 (fly ortholog of INTS11) is essential and expressed in the central nervous systems in a subset of neurons and most glia in larval and adult stages.
Mendeliome v1.836 SRSF1 Paul De Fazio gene: SRSF1 was added
gene: SRSF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SRSF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SRSF1 were set to 37071997
Phenotypes for gene: SRSF1 were set to Neurodevelopmental disorder, SRSF1-related MONDO:0700092
Review for gene: SRSF1 was set to GREEN
gene: SRSF1 was marked as current diagnostic
Added comment: 17 individuals from 16 families reported with mostly de novo variants. Variants were a mixture of missense, nonsense/frameshift (both NMD-predicted and not NMD-predicted) and microdeletions. In one family, only one parent was available for testing. In another family, 2 affected siblings had the variant but the variant was not identified in either parent suggesting germline mosaicism.

Functional testing of a subset of variants in Drosophila supported pathogenicity in most, but 2 missense variants showed no functional effect and were classified VUS. Episignature analysis (EpiSign) on patient DNA from blood showed a specific DNA methylation signature in patients with the variants classified pathogenic but not those classified VUS.

Phenotypes included mainly neurological abnormalities (mild to moderate ID/dev delay, motor delay, speech delay, and behavioural disorders) and facial dysmorphisms.

Other features included hypotonia (11/16), variable brain abnormalities on MRI (6/12), variable cardiac malformations (6/14). urogenital malformations e.g. hypospadias, cryptorchidism (6/13), scoliosis (5/17) and/or variable other skeletal abnormalities (10/17).
Sources: Literature
Mendeliome v1.836 INTS11 Seb Lunke Classified gene: INTS11 as Green List (high evidence)
Mendeliome v1.836 INTS11 Seb Lunke Gene: ints11 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.281 POLR1A Elena Savva Classified gene: POLR1A as Green List (high evidence)
Congenital Heart Defect v0.281 POLR1A Elena Savva Gene: polr1a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1844 POLR1A Elena Savva gene: POLR1A was added
gene: POLR1A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: POLR1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: POLR1A were set to PMID: 37075751
Phenotypes for gene: POLR1A were set to Acrofacial dysostosis, Cincinnati type MIM#616462
Review for gene: POLR1A was set to AMBER
Added comment: PMID: 37075751 - reports individuals with epilepsy but an infrequent occurrence, found in 1/4 of the cohort
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5216 INTS11 Melanie Marty gene: INTS11 was added
gene: INTS11 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: INTS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS11 were set to PMID: 37054711
Phenotypes for gene: INTS11 were set to Global developmental delay; launguage delay; intellectual disability; impaired motor development; brain atrophy
Review for gene: INTS11 was set to GREEN
Added comment: PMID: 37054711 - 15 individuals from 10 unrelated families with bi-allelic variants in INTS11 with global developmental and language delay, intellectual disability, impaired motor development, and brain atrophy.

Functional studies in Drosophila showed that dIntS11 (fly ortholog of INTS11) is essential and expressed in the central nervous systems in a subset of neurons and most glia in larval and adult stages.
Sources: Literature
Craniosynostosis v1.55 RARA Krithika Murali changed review comment from: PMID: 37086723 - a study of 526 probands with syndromic craniosynostosis and analysis of trio exome sequencing data.

The authors report 2 unrelated individuals with a similar phenotype and a recurrent de novo heterozygous missense RARA variant - c.865G>A; p.(Gly289Arg). Gain of function mechanism postulated. No functional studies. Gene encodes retinoic acid receptor with some phenotypic features overlapping with prenatal retionic acid teratogen exposure.

The variant is absent from gnomAD, major GS (125), highly conserved residue in the hormone receptor domain.

Both affected individuals had severe craniosynostosis (sagittal or bicoronal).

Other shared phenotypic features included:
- limb anomalies (rocker-bottom feet, bowing of the legs, and short uppe rand lower limbs)
- other craniofacial anomalies (microtia,conductive hearing loss, ankyloglossia, esotropia, hypo-plastic nasal bones, and oligodontia)
- renal dysplasia with cysts, tracheomalacia, pulmonary arterial hypertension, developmental delays, hypotonia, cryptorchidism, seizures, adrenal insufficiency
Sources: Literature; to: PMID: 37086723 - a study of 526 probands with syndromic craniosynostosis and analysis of trio exome sequencing data.

The authors report 2 unrelated individuals with a similar phenotype and a recurrent de novo heterozygous missense RARA variant - c.865G>A; p.(Gly289Arg). Gain of function mechanism postulated. No functional studies. Gene encodes retinoic acid receptor with some phenotypic features overlapping with prenatal retionic acid teratogen exposure.

The variant is absent from gnomAD, major GS (125), highly conserved residue in the hormone receptor domain.

Both affected individuals had severe craniosynostosis (sagittal or bicoronal).

Other shared phenotypic features included:
- limb anomalies (rocker-bottom feet, bowing of the legs, and short upper and lower limbs)
- other craniofacial anomalies (microtia,conductive hearing loss, ankyloglossia, esotropia, hypo-plastic nasal bones, and oligodontia)
- renal dysplasia with cysts, tracheomalacia, pulmonary arterial hypertension, developmental delays, hypotonia, cryptorchidism, seizures, adrenal insufficiency
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5216 SRSF1 Paul De Fazio edited their review of gene: SRSF1: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Craniosynostosis v1.55 RARA Krithika Murali changed review comment from: PMID: 37086723 - a study of 526 probands with syndromic craniosynostosis and analysis of exome sequencing data.

The authors report 2 unrelated individuals with a similar phenotype and a recurrent de novo heterozygous missense RARA variant - c.865G>A; p.(Gly289Arg). Gain of function mechanism postulated. No functional studies. Gene encodes retinoic acid receptor with some phenotypic features overlapping with prenatal retionic acid teratogen exposure.

The variant is absent from gnomAD, major GS (125), highly conserved residue in the hormone receptor domain.

Both affected individuals had severe craniosynostosis (sagittal or bicoronal).

Other shared phenotypic features included:
- limb anomalies (rocker-bottom feet, bowing of the legs, and short uppe rand lower limbs)
- other craniofacial anomalies (microtia,conductive hearing loss, ankyloglossia, esotropia, hypo-plastic nasal bones, and oligodontia)
- renal dysplasia with cysts, tracheomalacia, pulmonary arterial hypertension, developmental delays, hypotonia, cryptorchidism, seizures, adrenal insufficiency
Sources: Literature; to: PMID: 37086723 - a study of 526 probands with syndromic craniosynostosis and analysis of trio exome sequencing data.

The authors report 2 unrelated individuals with a similar phenotype and a recurrent de novo heterozygous missense RARA variant - c.865G>A; p.(Gly289Arg). Gain of function mechanism postulated. No functional studies. Gene encodes retinoic acid receptor with some phenotypic features overlapping with prenatal retionic acid teratogen exposure.

The variant is absent from gnomAD, major GS (125), highly conserved residue in the hormone receptor domain.

Both affected individuals had severe craniosynostosis (sagittal or bicoronal).

Other shared phenotypic features included:
- limb anomalies (rocker-bottom feet, bowing of the legs, and short uppe rand lower limbs)
- other craniofacial anomalies (microtia,conductive hearing loss, ankyloglossia, esotropia, hypo-plastic nasal bones, and oligodontia)
- renal dysplasia with cysts, tracheomalacia, pulmonary arterial hypertension, developmental delays, hypotonia, cryptorchidism, seizures, adrenal insufficiency
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5216 POLR1A Elena Savva Marked gene: POLR1A as ready
Intellectual disability syndromic and non-syndromic v0.5216 POLR1A Elena Savva Gene: polr1a has been classified as Red List (Low Evidence).
Craniosynostosis v1.55 RARA Krithika Murali gene: RARA was added
gene: RARA was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: RARA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RARA were set to PMID: 37086723
Phenotypes for gene: RARA were set to Craniosynostosis - MONDO:0015469
Review for gene: RARA was set to AMBER
Added comment: PMID: 37086723 - a study of 526 probands with syndromic craniosynostosis and analysis of exome sequencing data.

The authors report 2 unrelated individuals with a similar phenotype and a recurrent de novo heterozygous missense RARA variant - c.865G>A; p.(Gly289Arg). Gain of function mechanism postulated. No functional studies. Gene encodes retinoic acid receptor with some phenotypic features overlapping with prenatal retionic acid teratogen exposure.

The variant is absent from gnomAD, major GS (125), highly conserved residue in the hormone receptor domain.

Both affected individuals had severe craniosynostosis (sagittal or bicoronal).

Other shared phenotypic features included:
- limb anomalies (rocker-bottom feet, bowing of the legs, and short uppe rand lower limbs)
- other craniofacial anomalies (microtia,conductive hearing loss, ankyloglossia, esotropia, hypo-plastic nasal bones, and oligodontia)
- renal dysplasia with cysts, tracheomalacia, pulmonary arterial hypertension, developmental delays, hypotonia, cryptorchidism, seizures, adrenal insufficiency
Sources: Literature
Mitochondrial disease v0.864 MRPL39 Lilian Downie gene: MRPL39 was added
gene: MRPL39 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: MRPL39 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPL39 were set to PMID: 37133451
Phenotypes for gene: MRPL39 were set to Leigh Syndrome MONDO:0009723
Review for gene: MRPL39 was set to GREEN
Added comment: 3 unrelated individuals, confirmed variants in trans
Functional studies on patient fibroblasts
Multisystem disease, variable onset
2x infants with a clinical diagnosis of Leigh syndrome (congestive cardiac
failure, increased lactates, seizures, apnea, poor feeding, and global developmental delay, leading
to early death (< 1 year of age))
Adult with hypertrophic cardiomyopathy, lactic acidosis, ADHD
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5216 SRSF1 Paul De Fazio gene: SRSF1 was added
gene: SRSF1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SRSF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRSF1 were set to 37071997
Phenotypes for gene: SRSF1 were set to Neurodevelopmental disorder, SRSF1-related MONDO:0700092
Review for gene: SRSF1 was set to GREEN
gene: SRSF1 was marked as current diagnostic
Added comment: 17 individuals from 16 families reported with mostly de novo variants. Variants were a mixture of missense, nonsense/frameshift (both NMD-predicted and not NMD-predicted) and microdeletions. In one family, only one parent was available for testing. In another family, 2 affected siblings had the variant but the variant was not identified in either parent suggesting germline mosaicism.

Functional testing of a subset of variants in Drosophila supported pathogenicity in most, but 2 missense variants showed no functional effect and were classified VUS. Episignature analysis (EpiSign) on patient DNA from blood showed a specific DNA methylation signature in patients with the variants classified pathogenic but not those classified VUS.

Phenotypes included mainly neurological abnormalities (mild to moderate ID/dev delay, motor delay, speech delay, and behavioural disorders) and facial dysmorphisms.

Other features included hypotonia (11/16), variable brain abnormalities on MRI (6/12), variable cardiac malformations (6/14). urogenital malformations e.g. hypospadias, cryptorchidism (6/13), scoliosis (5/17) and/or variable other skeletal abnormalities (10/17).
Sources: Literature
Congenital Heart Defect v0.280 POLR1A Elena Savva Marked gene: POLR1A as ready
Congenital Heart Defect v0.280 POLR1A Elena Savva Gene: polr1a has been classified as Red List (Low Evidence).
Mendeliome v1.835 SLC30A9 Zornitza Stark Marked gene: SLC30A9 as ready
Mendeliome v1.835 SLC30A9 Zornitza Stark Gene: slc30a9 has been classified as Green List (High Evidence).
Photosensitivity Syndromes v1.5 DNA2 Seb Lunke Marked gene: DNA2 as ready
Photosensitivity Syndromes v1.5 DNA2 Seb Lunke Gene: dna2 has been classified as Amber List (Moderate Evidence).
Photosensitivity Syndromes v1.5 DNA2 Seb Lunke Classified gene: DNA2 as Amber List (moderate evidence)
Photosensitivity Syndromes v1.5 DNA2 Seb Lunke Gene: dna2 has been classified as Amber List (Moderate Evidence).
Cataract v0.354 DNA2 Seb Lunke Classified gene: DNA2 as Amber List (moderate evidence)
Cataract v0.354 DNA2 Seb Lunke Gene: dna2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.835 SLC30A9 Zornitza Stark Classified gene: SLC30A9 as Green List (high evidence)
Mendeliome v1.835 SLC30A9 Zornitza Stark Gene: slc30a9 has been classified as Green List (High Evidence).
Cataract v0.353 DNA2 Seb Lunke Marked gene: DNA2 as ready
Cataract v0.353 DNA2 Seb Lunke Gene: dna2 has been classified as Red List (Low Evidence).
Photosensitivity Syndromes v1.4 DNA2 Seb Lunke gene: DNA2 was added
gene: DNA2 was added to Photosensitivity Syndromes. Sources: Literature
deep intronic, founder tags were added to gene: DNA2.
Mode of inheritance for gene: DNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNA2 were set to 37133451
Phenotypes for gene: DNA2 were set to Rothmund-Thomson syndrome, MONDO:0010002, DNA2 associated
Review for gene: DNA2 was set to AMBER
Added comment: A phenotypic expansion has been proposed based on a cohort of six Brazilian probands that in addition to classic RTS also presented with poikiloderma and congenital cataracts. All shared the same deep intronic splice variant, c.588–2214 A>G, in trans with other LoF variants. The deep intronic variant has been shown to result in the inclusion of a cryptic exon in the mature RNA, resulting in a frame shift and premature termination codon. The authors speculate that the shared intronic variant, which they attribute to a founder effect, has residual normal splicing responsible for the phenotypic variation.
Sources: Literature
Dystonia - complex v0.223 SLC30A9 Zornitza Stark Marked gene: SLC30A9 as ready
Dystonia - complex v0.223 SLC30A9 Zornitza Stark Gene: slc30a9 has been classified as Green List (High Evidence).
Mendeliome v1.834 SLC30A9 Lucy Spencer gene: SLC30A9 was added
gene: SLC30A9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC30A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A9 were set to 37041080
Phenotypes for gene: SLC30A9 were set to Birk-Landau-Perez syndrome (MIM#617595)
Review for gene: SLC30A9 was set to GREEN
Added comment: PMID:37041080 - 2 families previously reported and this paper describes 4 more with biallelic SLC30A9 variants. Original 2 families: 6 affected members all hom for Ala350del, and 1 affected member chet for 2 frameshifts. 4 families from this paper: 2 families have the same homozygous missense (Gly418Val), family 3 has 4 affected sibs hom for Ala350del, family 4 1 affected chet for a frameshift and a synonymous. So 2 fams homs for Ala350del and 2 fams hom for Gly418Val.
All have Brik-Landau-Perez syndrome: all with ID, movement disorder and dystonia, and many with oculomotor apraxia, renal abnormalitie, ptosis, some had hearing impairment.
Sources: Literature
Lymphoedema_nonsyndromic v0.33 ERG Ain Roesley Classified gene: ERG as Green List (high evidence)
Lymphoedema_nonsyndromic v0.33 ERG Ain Roesley Gene: erg has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5216 POLR1A Elena Savva gene: POLR1A was added
gene: POLR1A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: POLR1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: POLR1A were set to PMID: 37075751
Phenotypes for gene: POLR1A were set to Acrofacial dysostosis, Cincinnati type MIM#616462
Review for gene: POLR1A was set to GREEN
Added comment: PMID: 37075751 - >10 patients with developmental delay
Sources: Literature
Dystonia - complex v0.223 SLC30A9 Zornitza Stark Classified gene: SLC30A9 as Green List (high evidence)
Dystonia - complex v0.223 SLC30A9 Zornitza Stark Gene: slc30a9 has been classified as Green List (High Evidence).
Lymphoedema_nonsyndromic v0.33 ERG Ain Roesley Classified gene: ERG as Green List (high evidence)
Lymphoedema_nonsyndromic v0.33 ERG Ain Roesley Gene: erg has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5216 SLC30A9 Zornitza Stark Classified gene: SLC30A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5216 SLC30A9 Zornitza Stark Gene: slc30a9 has been classified as Green List (High Evidence).
Cataract v0.353 DNA2 Seb Lunke gene: DNA2 was added
gene: DNA2 was added to Cataract. Sources: Literature
Mode of inheritance for gene: DNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNA2 were set to 37133451
Phenotypes for gene: DNA2 were set to Rothmund-Thomson syndrome, MONDO:0010002, DNA2 associated
Review for gene: DNA2 was set to AMBER
Added comment: A phenotypic expansion has been proposed based on a cohort of six Brazilian probands that in addition to classic RTS also presented with poikiloderma and congenital cataracts. All shared the same deep intronic splice variant, c.588–2214 A>G, in trans with other LoF variants. The deep intronic variant has been shown to result in the inclusion of a cryptic exon in the mature RNA, resulting in a frame shift and premature termination codon. The authors speculate that the shared intronic variant, which they attribute to a founder effect, has residual normal splicing responsible for the phenotypic variation.
Sources: Literature
Lymphoedema_nonsyndromic v0.33 ERG Ain Roesley Classified gene: ERG as Green List (high evidence)
Lymphoedema_nonsyndromic v0.33 ERG Ain Roesley Gene: erg has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5216 SLC30A9 Zornitza Stark Marked gene: SLC30A9 as ready
Intellectual disability syndromic and non-syndromic v0.5216 SLC30A9 Zornitza Stark Gene: slc30a9 has been classified as Green List (High Evidence).
Lymphoedema_nonsyndromic v0.33 ERG Ain Roesley Classified gene: ERG as Green List (high evidence)
Lymphoedema_nonsyndromic v0.33 ERG Ain Roesley Gene: erg has been classified as Green List (High Evidence).
Mendeliome v1.834 GPR156 Anna Ritchie gene: GPR156 was added
gene: GPR156 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPR156 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPR156 were set to PMID: 36928819
Phenotypes for gene: GPR156 were set to Sensorineural hearing loss, MONDO:60700002, GPR156-related
Review for gene: GPR156 was set to GREEN
Added comment: Eight affected individuals from three unrelated families with congenital nonsyndromic bilateral sensorineural hearing loss. Homozygous or compound heterozygous loss of function variants were reported in these families.
Sources: Literature
Optic Atrophy v1.12 MCAT Belinda Chong reviewed gene: MCAT: Rating: AMBER; Mode of pathogenicity: None; Publications: 33918393, 31915829; Phenotypes: Progressive autosomal recessive optic neuropathy, Leber hereditary optic neuropathy (LHON)-like; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5216 SLC30A9 Zornitza Stark Classified gene: SLC30A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5216 SLC30A9 Zornitza Stark Gene: slc30a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5216 SLC30A9 Zornitza Stark Classified gene: SLC30A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5216 SLC30A9 Zornitza Stark Gene: slc30a9 has been classified as Green List (High Evidence).
Cataract v0.353 DNA2 Seb Lunke gene: DNA2 was added
gene: DNA2 was added to Cataract. Sources: Literature
deep intronic, founder tags were added to gene: DNA2.
Mode of inheritance for gene: DNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNA2 were set to 37133451
Phenotypes for gene: DNA2 were set to Rothmund-Thomson syndrome, MONDO:0010002, DNA2 associated
Review for gene: DNA2 was set to AMBER
Added comment: A phenotypic expansion has been proposed based on a cohort of six Brazilian probands that in addition to classic RTS also presented with poikiloderma and congenital cataracts. All shared the same deep intronic splice variant, c.588–2214 A>G, in trans with other LoF variants. The deep intronic variant has been shown to result in the inclusion of a cryptic exon in the mature RNA, resulting in a frame shift and premature termination codon. The authors speculate that the shared intronic variant, which they attribute to a founder effect, has residual normal splicing responsible for the phenotypic variation.
Sources: Literature
Congenital Heart Defect v0.280 POLR1A Elena Savva gene: POLR1A was added
gene: POLR1A was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: POLR1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: POLR1A were set to PMID: 37075751
Phenotypes for gene: POLR1A were set to Acrofacial dysostosis, Cincinnati type MIM#616462
Review for gene: POLR1A was set to GREEN
Added comment: PMID: 37075751 - 8/21 patients had congenital heart disease (mostly septal defect, one patient had bicuspid aortic valve, aortic aneurysm). Het mouse model had heart defects including truncus arteriosus
Sources: Literature
Lymphoedema_nonsyndromic v0.33 ERG Ain Roesley Classified gene: ERG as Green List (high evidence)
Lymphoedema_nonsyndromic v0.33 ERG Ain Roesley Gene: erg has been classified as Green List (High Evidence).
Mendeliome v1.834 MRPL39 Lilian Downie changed review comment from: AR
3 unrelated individuals, confirmed variants in trans
Functional studies on patient fibroblasts
Multisystem disease, variable onset
2x infants with a clinical diagnosis of Leigh syndrome (MIM 256000)
Adult with hypertrophic cardiomyopathy, lactic acidosis, ADHD
Sources: Literature; to: AR
3 unrelated individuals, confirmed variants in trans
Functional studies on patient fibroblasts
Multisystem disease, variable onset
2x infants with a clinical diagnosis of Leigh syndrome (congestive cardiac
failure, increased lactates, seizures, apnea, poor feeding, and global developmental delay, leading
to early death (< 1 year of age))
Adult with hypertrophic cardiomyopathy, lactic acidosis, ADHD
Sources: Literature
Mendeliome v1.834 DPP9 Sarah Pantaleo reviewed gene: DPP9: Rating: GREEN; Mode of pathogenicity: None; Publications: 36112693; Phenotypes: Hatipoglu immunodeficiency syndrome MIM#620331; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lymphoedema_nonsyndromic v0.32 ERG Ain Roesley Marked gene: ERG as ready
Lymphoedema_nonsyndromic v0.32 ERG Ain Roesley Gene: erg has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.280 POLR1A Elena Savva gene: POLR1A was added
gene: POLR1A was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: POLR1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: POLR1A were set to PMID: 37075751
Phenotypes for gene: POLR1A were set to Acrofacial dysostosis, Cincinnati type MIM#616462
Review for gene: POLR1A was set to GREEN
Added comment: PMID: 37075751 - 8/21 patients had congenital heart disease (mostly septal defect, one patient had bicuspid aortic valve, aortic aneurysm). Het mouse model had heart defects including truncus arteriosus
Sources: Literature
Mendeliome v1.834 MRPL39 Lilian Downie gene: MRPL39 was added
gene: MRPL39 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MRPL39 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPL39 were set to PMID: 37133451
Phenotypes for gene: MRPL39 were set to Leigh syndrome MONDO:0009723
Added comment: AR
3 unrelated individuals, confirmed variants in trans
Functional studies on patient fibroblasts
Multisystem disease, variable onset
2x infants with a clinical diagnosis of Leigh syndrome (MIM 256000)
Adult with hypertrophic cardiomyopathy, lactic acidosis, ADHD
Sources: Literature
Lymphoedema_nonsyndromic v0.32 ERG Ain Roesley gene: ERG was added
gene: ERG was added to Lymphoedema_nonsyndromic. Sources: Literature
Mode of inheritance for gene: ERG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ERG were set to 36928819
Phenotypes for gene: ERG were set to primary lymphoedema MONDO#0019175, ERG-related
Penetrance for gene: ERG were set to unknown
Review for gene: ERG was set to GREEN
gene: ERG was marked as current diagnostic
Added comment: 3 families with fs variants
2x NMD = 1x de novo + 1x mosaic father
1x protein truncating = 2 affected siblings with an unaffected father who wasn't sequenced

4th family with protein truncating variant but has other clinical features and lymphoedema was only identified upon chart review

over expression of mutant cDNA demonstrated mislocalisation into the cytoplasm
Sources: Literature
Mendeliome v1.834 INTS11 Melanie Marty reviewed gene: INTS11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37054711; Phenotypes: Global developmental delay, launguage delay, intellectual disability, impaired motor development, brain atrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autoinflammatory Disorders v1.4 DPP9 Sarah Pantaleo reviewed gene: DPP9: Rating: GREEN; Mode of pathogenicity: None; Publications: 36112693; Phenotypes: Hatipoglu immunodeficiency syndrome MIM#620331; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.222 SLC30A9 Lucy Spencer gene: SLC30A9 was added
gene: SLC30A9 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: SLC30A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A9 were set to 37041080
Phenotypes for gene: SLC30A9 were set to Birk-Landau-Perez syndrome (MIM#617595)
Review for gene: SLC30A9 was set to GREEN
Added comment: PMID:37041080 - 2 families previously reported and this paper describes 4 more with biallelic SLC30A9 variants. Original 2 families: 6 affected members all hom for Ala350del, and 1 affected member chet for 2 frameshifts. 4 families from this paper: 2 families have the same homozygous missense (Gly418Val), family 3 has 4 affected sibs hom for Ala350del, family 4 1 affected chet for a frameshift and a synonymous. So 2 fams homs for Ala350del and 2 fams hom for Gly418Val.
All have Brik-Landau-Perez syndrome: all with ID, movement disorder and dystonia, and many with oculomotor apraxia, renal abnormalitie, ptosis, some had hearing impairment.
Sources: Literature
Clefting disorders v0.196 POLR1A Elena Savva Marked gene: POLR1A as ready
Clefting disorders v0.196 POLR1A Elena Savva Gene: polr1a has been classified as Green List (High Evidence).
Craniosynostosis v1.55 POLR1A Elena Savva Marked gene: POLR1A as ready
Craniosynostosis v1.55 POLR1A Elena Savva Gene: polr1a has been classified as Amber List (Moderate Evidence).
Craniosynostosis v1.55 POLR1A Elena Savva Classified gene: POLR1A as Amber List (moderate evidence)
Craniosynostosis v1.55 POLR1A Elena Savva Gene: polr1a has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.196 POLR1A Elena Savva Phenotypes for gene: POLR1A were changed from cleft palte to Acrofacial dysostosis, Cincinnati type MIM#616462
Clefting disorders v0.195 POLR1A Elena Savva Classified gene: POLR1A as Green List (high evidence)
Clefting disorders v0.195 POLR1A Elena Savva Gene: polr1a has been classified as Green List (High Evidence).
Clefting disorders v0.194 POLR1A Elena Savva reviewed gene: POLR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37075751; Phenotypes: Acrofacial dysostosis, Cincinnati type MIM#616462; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.834 ERG Ain Roesley Publications for gene: ERG were set to
Craniosynostosis v1.54 POLR1A Elena Savva gene: POLR1A was added
gene: POLR1A was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: POLR1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: POLR1A were set to PMID: 37075751
Phenotypes for gene: POLR1A were set to Acrofacial dysostosis, Cincinnati type MIM#616462
Review for gene: POLR1A was set to AMBER
Added comment: PMID: 37075751 - craniosynostosis shown in 3/21 patients
Sources: Literature
Fetal anomalies v1.106 GATAD2A Zornitza Stark Marked gene: GATAD2A as ready
Fetal anomalies v1.106 GATAD2A Zornitza Stark Gene: gatad2a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.106 GATAD2A Zornitza Stark Classified gene: GATAD2A as Amber List (moderate evidence)
Fetal anomalies v1.106 GATAD2A Zornitza Stark Gene: gatad2a has been classified as Amber List (Moderate Evidence).
Mendeliome v1.833 ERG Ain Roesley Phenotypes for gene: ERG were changed from to primary lymphoedema MONDO#0019175, ERG-related
Mendeliome v1.832 ERG Ain Roesley Mode of inheritance for gene: ERG was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.832 ERG Ain Roesley Classified gene: ERG as Green List (high evidence)
Mendeliome v1.832 ERG Ain Roesley Gene: erg has been classified as Green List (High Evidence).
Mendeliome v1.831 ERG Ain Roesley reviewed gene: ERG: Rating: GREEN; Mode of pathogenicity: None; Publications: 36928819; Phenotypes: primary lymphoedema MONDO#0019175, ERG-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v1.105 GATAD2A Zornitza Stark gene: GATAD2A was added
gene: GATAD2A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GATAD2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GATAD2A were set to https://doi.org/10.1016/j.xhgg.2023.100198; 17565372
Phenotypes for gene: GATAD2A were set to Neurodevelopmental disorder, MONDO:0700092, GATAD2A-related
Review for gene: GATAD2A was set to AMBER
Added comment: Inconsistent pattern of congenital abnormalities.

https://doi.org/10.1016/j.xhgg.2023.100198 - Five unrelated individuals with a neurodevelopmental disorder identified with 3 missense & 2 LoF (4 de novo & 1 unknown inheritance). The shared clinical features with variable expressivity include global developmental delay (4/4), craniofacial dysmorphism (3/5), structural brain defects (2/3), musculoskeletal anomalies (3/5), vision/hearing defects (2/3), gastrointestinal/renal defects (2/3). Loss of function is the expected mechanism of disease. In vitro assays of one of the missense variants (p.Cys420Tyr) demonstrates disruption of GATAD2A integration with CHD3, CHD4, and CHD5
PMID: 17565372 - null mouse model is embryonic lethal.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5215 SLC30A9 Lucy Spencer gene: SLC30A9 was added
gene: SLC30A9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SLC30A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A9 were set to 37041080
Phenotypes for gene: SLC30A9 were set to Birk-Landau-Perez syndrome (MIM#617595)
Review for gene: SLC30A9 was set to GREEN
Added comment: PMID:37041080 - 2 families previously reported and this paper describes 4 more with biallelic SLC30A9 variants. Original 2 families: 6 affected members all hom for Ala350del, and 1 affected member chet for 2 frameshifts. 4 families from this paper: 2 families have the same homozygous missense (Gly418Val), family 3 has 4 affected sibs hom for Ala350del, family 4 1 affected chet for a frameshift and a synonymous. So 2 fams homs for Ala350del and 2 fams hom for Gly418Val.
All have Brik-Landau-Perez syndrome: all with ID, movement disorder and dystonia, and many with oculomotor apraxia, renal abnormalitie, ptosis, some had hearing impairment.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5215 GATAD2A Bryony Thompson Marked gene: GATAD2A as ready
Intellectual disability syndromic and non-syndromic v0.5215 GATAD2A Bryony Thompson Gene: gatad2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5215 GATAD2A Bryony Thompson Classified gene: GATAD2A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5215 GATAD2A Bryony Thompson Gene: gatad2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5214 GATAD2A Bryony Thompson gene: GATAD2A was added
gene: GATAD2A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GATAD2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GATAD2A were set to https://doi.org/10.1016/j.xhgg.2023.100198; 17565372
Phenotypes for gene: GATAD2A were set to Neurodevelopmental disorder, MONDO:0700092, GATAD2A-related
Review for gene: GATAD2A was set to GREEN
Added comment: https://doi.org/10.1016/j.xhgg.2023.100198 - Five unrelated individuals with a neurodevelopmental disorder identified with 3 missense & 2 LoF (4 de novo & 1 unknown inheritance). The shared clinical features with variable expressivity include global developmental delay (4/4), craniofacial dysmorphism (3/5), structural brain defects (2/3), musculoskeletal anomalies (3/5), vision/hearing defects (2/3), gastrointestinal/renal defects (2/3). Loss of function is the expected mechanism of disease. In vitro assays of one of the missense variants (p.Cys420Tyr) demonstrates disruption of GATAD2A integration with CHD3, CHD4, and CHD5
PMID: 17565372 - null mouse model is embryonic lethal.
Sources: Literature
Mendeliome v1.831 GATAD2A Bryony Thompson Marked gene: GATAD2A as ready
Mendeliome v1.831 GATAD2A Bryony Thompson Gene: gatad2a has been classified as Green List (High Evidence).
Mendeliome v1.831 GATAD2A Bryony Thompson Classified gene: GATAD2A as Green List (high evidence)
Mendeliome v1.831 GATAD2A Bryony Thompson Gene: gatad2a has been classified as Green List (High Evidence).
Mendeliome v1.830 GATAD2A Bryony Thompson gene: GATAD2A was added
gene: GATAD2A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GATAD2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GATAD2A were set to https://doi.org/10.1016/j.xhgg.2023.100198; 17565372
Phenotypes for gene: GATAD2A were set to Neurodevelopmental disorder, MONDO:0700092, GATAD2A-related
Review for gene: GATAD2A was set to GREEN
Added comment: https://doi.org/10.1016/j.xhgg.2023.100198 - Five unrelated individuals with a neurodevelopmental disorder identified with 3 missense & 2 LoF (4 de novo & 1 unknown inheritance). The shared clinical features with variable expressivity include global developmental delay (4/4), craniofacial dysmorphism (3/5), structural brain defects (2/3), musculoskeletal anomalies (3/5), vision/hearing defects (2/3), gastrointestinal/renal defects (2/3). Loss of function is the expected mechanism of disease. In vitro assays of one of the missense variants (p.Cys420Tyr) demonstrates disruption of GATAD2A integration with CHD3, CHD4, and CHD5
PMID: 17565372 - null mouse model is embryonic lethal.
Sources: Literature
Mendeliome v1.829 RNF212B Bryony Thompson Publications for gene: RNF212B were set to https://doi.org/10.1016/j.xhgg.2023.100189
Brain Calcification v1.76 TRPM6 Yetong Chen gene: TRPM6 was added
gene: TRPM6 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: TRPM6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPM6 were set to 22982920
Phenotypes for gene: TRPM6 were set to Hypomagnesemia 1, intestinal, MIM# 602014
Review for gene: TRPM6 was set to RED
Added comment: Insufficient evidence supports the gene-disease association.
PMID 22982920 reports a patient with a novel homozygous variant (ins 2999T) of the TRPM6 gene who had bilateral basal ganglia calci­fication. The authors state that brain calcification has never been reported in hypomagnesemia patients before.
Sources: Expert list
Brain Calcification v1.76 TREX1 Yetong Chen reviewed gene: TREX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34949589, 26581299, 29386495; Phenotypes: Aicardi-Goutieres syndrome 1, dominant and recessive, MIM# 225750; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Brain Calcification v1.76 TREM2 Yetong Chen reviewed gene: TREM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33969597, 35705056; Phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.170 LIG4 Zornitza Stark Marked gene: LIG4 as ready
Disorders of immune dysregulation v0.170 LIG4 Zornitza Stark Gene: lig4 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.170 LIG4 Zornitza Stark Phenotypes for gene: LIG4 were changed from Immune dysregulation to LIG4 syndrome, MIM# 606593; Immune dysregulation
Disorders of immune dysregulation v0.169 LIG4 Zornitza Stark Classified gene: LIG4 as Green List (high evidence)
Disorders of immune dysregulation v0.169 LIG4 Zornitza Stark Gene: lig4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5213 KDM5A Zornitza Stark Marked gene: KDM5A as ready
Intellectual disability syndromic and non-syndromic v0.5213 KDM5A Zornitza Stark Gene: kdm5a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5213 KDM5A Zornitza Stark Classified gene: KDM5A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5213 KDM5A Zornitza Stark Gene: kdm5a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5212 KDM5A Zornitza Stark gene: KDM5A was added
gene: KDM5A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KDM5A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KDM5A were set to 21937992; 33350388
Phenotypes for gene: KDM5A were set to Neurodevelopmental disorder MONDO:0700092, KDM5A-related
Review for gene: KDM5A was set to GREEN
Added comment: PMID:21937992 reported a family with recessive missense KDM5A variant presenting with an undefined developmental disorder characterised with intellectual disability and facial dysmorphisms.

PMID:33350388 reported nine patients from seven unrelated families identified with variants in KDM5A, of which three unrelated patients harboured heterozygous variants, while six patients from four unrelated families had homozygous variants. These patients presented with autism spectrum disorder (ASD) and a spectrum of neurodevelopmental phenotypes including intellectual disability, lack of speech, developmental delay and motor impairment.

In addition, loss of KDM5A has resulted in repetitive behaviors, sociability deficits, cognitive dysfunction, and abnormal dendritic morphogenesis in mice.

This gene has already been associated with phenotype in Gene2Phenotype (biallelic inheritance with 'limited' rating), but not in OMIM.
Sources: Literature
Mendeliome v1.828 KDM5A Zornitza Stark Marked gene: KDM5A as ready
Mendeliome v1.828 KDM5A Zornitza Stark Gene: kdm5a has been classified as Green List (High Evidence).
Mendeliome v1.828 KDM5A Zornitza Stark Classified gene: KDM5A as Green List (high evidence)
Mendeliome v1.828 KDM5A Zornitza Stark Gene: kdm5a has been classified as Green List (High Evidence).
Craniosynostosis v1.53 BCL11B Zornitza Stark Marked gene: BCL11B as ready
Craniosynostosis v1.53 BCL11B Zornitza Stark Gene: bcl11b has been classified as Green List (High Evidence).
Craniosynostosis v1.53 BCL11B Zornitza Stark Phenotypes for gene: BCL11B were changed from Craniosynostosis to Craniosynostosis, MONDO:0015469, BCL11B-related
Craniosynostosis v1.52 BCL11B Zornitza Stark Classified gene: BCL11B as Green List (high evidence)
Craniosynostosis v1.52 BCL11B Zornitza Stark Gene: bcl11b has been classified as Green List (High Evidence).
Craniosynostosis v1.51 NFIA Zornitza Stark Marked gene: NFIA as ready
Craniosynostosis v1.51 NFIA Zornitza Stark Gene: nfia has been classified as Green List (High Evidence).
Craniosynostosis v1.51 NFIA Zornitza Stark Phenotypes for gene: NFIA were changed from Craniosynostosis to Craniosynostosis MONDO:0015469, NFIA-related
Craniosynostosis v1.50 NFIA Zornitza Stark Classified gene: NFIA as Green List (high evidence)
Craniosynostosis v1.50 NFIA Zornitza Stark Gene: nfia has been classified as Green List (High Evidence).
Craniosynostosis v1.49 NFIA Zornitza Stark reviewed gene: NFIA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniosynostosis MONDO:0015469, NFIA-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v1.49 PRRX1 Zornitza Stark Marked gene: PRRX1 as ready
Craniosynostosis v1.49 PRRX1 Zornitza Stark Gene: prrx1 has been classified as Green List (High Evidence).
Craniosynostosis v1.49 PRRX1 Zornitza Stark Phenotypes for gene: PRRX1 were changed from Craniosynostosis to Craniosynostosis, MONDO:0015469, PRRX1-related
Craniosynostosis v1.48 PRRX1 Zornitza Stark Classified gene: PRRX1 as Green List (high evidence)
Craniosynostosis v1.48 PRRX1 Zornitza Stark Gene: prrx1 has been classified as Green List (High Evidence).
Mendeliome v1.827 YWHAE Zornitza Stark Marked gene: YWHAE as ready
Mendeliome v1.827 YWHAE Zornitza Stark Gene: ywhae has been classified as Green List (High Evidence).
Mendeliome v1.827 YWHAE Zornitza Stark Classified gene: YWHAE as Green List (high evidence)
Mendeliome v1.827 YWHAE Zornitza Stark Gene: ywhae has been classified as Green List (High Evidence).
Mendeliome v1.826 YWHAE Zornitza Stark gene: YWHAE was added
gene: YWHAE was added to Mendeliome. Sources: Literature
SV/CNV tags were added to gene: YWHAE.
Mode of inheritance for gene: YWHAE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: YWHAE were set to 36999555
Phenotypes for gene: YWHAE were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: YWHAE was set to GREEN
Added comment: PMID 36999555 reports 10 patients with YWHAE variants (1 intragenic deletion and 5 large deletions encompassing YWHEA but not PAFAH1B1) who have mild to severe intellectual disability. 3 individuals with SNVs. Mouse model supports gene-disease association.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5211 YWHAE Zornitza Stark Marked gene: YWHAE as ready
Intellectual disability syndromic and non-syndromic v0.5211 YWHAE Zornitza Stark Gene: ywhae has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5211 YWHAE Zornitza Stark Classified gene: YWHAE as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5211 YWHAE Zornitza Stark Gene: ywhae has been classified as Green List (High Evidence).
Callosome v0.489 YWHAE Zornitza Stark Marked gene: YWHAE as ready
Callosome v0.489 YWHAE Zornitza Stark Gene: ywhae has been classified as Green List (High Evidence).
Callosome v0.489 YWHAE Zornitza Stark Classified gene: YWHAE as Green List (high evidence)
Callosome v0.489 YWHAE Zornitza Stark Gene: ywhae has been classified as Green List (High Evidence).
Brain Calcification v1.76 TINF2 Yetong Chen reviewed gene: TINF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33734615, 32966588, 28095086; Phenotypes: Dyskeratosis congenita, autosomal dominant 3, MIM# 613990; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v1.76 PANK2 Zornitza Stark Marked gene: PANK2 as ready
Brain Calcification v1.76 PANK2 Zornitza Stark Gene: pank2 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.76 PANK2 Zornitza Stark Classified gene: PANK2 as Amber List (moderate evidence)
Brain Calcification v1.76 PANK2 Zornitza Stark Gene: pank2 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.75 PANK2 Zornitza Stark reviewed gene: PANK2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with brain iron accumulation 1, MIM# 234200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.75 PANK2 Zornitza Stark Classified gene: PANK2 as Red List (low evidence)
Brain Calcification v1.75 PANK2 Zornitza Stark Gene: pank2 has been classified as Red List (Low Evidence).
Brain Calcification v1.74 PCDH12 Zornitza Stark Marked gene: PCDH12 as ready
Brain Calcification v1.74 PCDH12 Zornitza Stark Gene: pcdh12 has been classified as Green List (High Evidence).
Brain Calcification v1.74 PCDH12 Zornitza Stark Classified gene: PCDH12 as Green List (high evidence)
Brain Calcification v1.74 PCDH12 Zornitza Stark Gene: pcdh12 has been classified as Green List (High Evidence).
Brain Calcification v1.73 PSMB8 Zornitza Stark Marked gene: PSMB8 as ready
Brain Calcification v1.73 PSMB8 Zornitza Stark Gene: psmb8 has been classified as Red List (Low Evidence).
Brain Calcification v1.73 PSMB8 Zornitza Stark Classified gene: PSMB8 as Red List (low evidence)
Brain Calcification v1.73 PSMB8 Zornitza Stark Gene: psmb8 has been classified as Red List (Low Evidence).
Brain Calcification v1.72 PSMG2 Zornitza Stark Classified gene: PSMG2 as Red List (low evidence)
Brain Calcification v1.72 PSMG2 Zornitza Stark Gene: psmg2 has been classified as Red List (Low Evidence).
Brain Calcification v1.71 PTH Zornitza Stark Marked gene: PTH as ready
Brain Calcification v1.71 PTH Zornitza Stark Gene: pth has been classified as Red List (Low Evidence).
Brain Calcification v1.71 PTH Zornitza Stark Classified gene: PTH as Red List (low evidence)
Brain Calcification v1.71 PTH Zornitza Stark Gene: pth has been classified as Red List (Low Evidence).
Brain Calcification v1.71 PTS Zornitza Stark Marked gene: PTS as ready
Brain Calcification v1.71 PTS Zornitza Stark Gene: pts has been classified as Red List (Low Evidence).
Brain Calcification v1.71 PTS Zornitza Stark Classified gene: PTS as Red List (low evidence)
Brain Calcification v1.71 PTS Zornitza Stark Gene: pts has been classified as Red List (Low Evidence).
Brain Calcification v1.70 QDPR Zornitza Stark Marked gene: QDPR as ready
Brain Calcification v1.70 QDPR Zornitza Stark Gene: qdpr has been classified as Red List (Low Evidence).
Brain Calcification v1.70 QDPR Zornitza Stark Classified gene: QDPR as Red List (low evidence)
Brain Calcification v1.70 QDPR Zornitza Stark Gene: qdpr has been classified as Red List (Low Evidence).
Brain Calcification v1.69 GNA11 Zornitza Stark Marked gene: GNA11 as ready
Brain Calcification v1.69 GNA11 Zornitza Stark Gene: gna11 has been classified as Red List (Low Evidence).
Brain Calcification v1.69 GNA11 Zornitza Stark Classified gene: GNA11 as Red List (low evidence)
Brain Calcification v1.69 GNA11 Zornitza Stark Gene: gna11 has been classified as Red List (Low Evidence).
Brain Calcification v1.68 GLA Zornitza Stark Marked gene: GLA as ready
Brain Calcification v1.68 GLA Zornitza Stark Gene: gla has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.68 GLA Zornitza Stark Classified gene: GLA as Amber List (moderate evidence)
Brain Calcification v1.68 GLA Zornitza Stark Gene: gla has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.67 GCM2 Zornitza Stark Marked gene: GCM2 as ready
Brain Calcification v1.67 GCM2 Zornitza Stark Gene: gcm2 has been classified as Green List (High Evidence).
Brain Calcification v1.67 GCM2 Zornitza Stark Classified gene: GCM2 as Green List (high evidence)
Brain Calcification v1.67 GCM2 Zornitza Stark Gene: gcm2 has been classified as Green List (High Evidence).
Brain Calcification v1.66 FOLR1 Zornitza Stark Marked gene: FOLR1 as ready
Brain Calcification v1.66 FOLR1 Zornitza Stark Gene: folr1 has been classified as Red List (Low Evidence).
Brain Calcification v1.66 GATA3 Zornitza Stark Marked gene: GATA3 as ready
Brain Calcification v1.66 GATA3 Zornitza Stark Gene: gata3 has been classified as Green List (High Evidence).
Brain Calcification v1.66 GATA3 Zornitza Stark Classified gene: GATA3 as Green List (high evidence)
Brain Calcification v1.66 GATA3 Zornitza Stark Gene: gata3 has been classified as Green List (High Evidence).
Brain Calcification v1.65 FOLR1 Zornitza Stark Phenotypes for gene: FOLR1 were changed from to Neurodegeneration due to cerebral folate transport deficiency, MIM# 613068
Brain Calcification v1.64 FAM20C Zornitza Stark Marked gene: FAM20C as ready
Brain Calcification v1.64 FAM20C Zornitza Stark Gene: fam20c has been classified as Green List (High Evidence).
Brain Calcification v1.64 FAM20C Zornitza Stark Publications for gene: FAM20C were set to 27862258; 20825432; 36914045; 34259997; 32299476; 29341424
Brain Calcification v1.63 FAM20C Zornitza Stark Publications for gene: FAM20C were set to 27862258; 20825432
Brain Calcification v1.63 FOLR1 Zornitza Stark Classified gene: FOLR1 as Red List (low evidence)
Brain Calcification v1.63 FOLR1 Zornitza Stark Gene: folr1 has been classified as Red List (Low Evidence).
Brain Calcification v1.62 FAM20C Zornitza Stark Classified gene: FAM20C as Green List (high evidence)
Brain Calcification v1.62 FAM20C Zornitza Stark Gene: fam20c has been classified as Green List (High Evidence).
Brain Calcification v1.61 SUOX Zornitza Stark Marked gene: SUOX as ready
Brain Calcification v1.61 SUOX Zornitza Stark Gene: suox has been classified as Green List (High Evidence).
Brain Calcification v1.61 FAM20C Zornitza Stark reviewed gene: FAM20C: Rating: GREEN; Mode of pathogenicity: None; Publications: 36914045, 34259997, 32299476, 29341424; Phenotypes: Raine syndrome, MIM# 259775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.61 SUOX Zornitza Stark Classified gene: SUOX as Green List (high evidence)
Brain Calcification v1.61 SUOX Zornitza Stark Gene: suox has been classified as Green List (High Evidence).
Brain Calcification v1.60 TBC1D20 Zornitza Stark Marked gene: TBC1D20 as ready
Brain Calcification v1.60 TBC1D20 Zornitza Stark Gene: tbc1d20 has been classified as Red List (Low Evidence).
Brain Calcification v1.60 TBC1D20 Zornitza Stark Phenotypes for gene: TBC1D20 were changed from Cerebroretinal microangiopathy with calcifications and cysts 2, MIM# 617341 to Warburg micro syndrome 4, MIM# 615663
Brain Calcification v1.59 TBC1D20 Zornitza Stark Classified gene: TBC1D20 as Red List (low evidence)
Brain Calcification v1.59 TBC1D20 Zornitza Stark Gene: tbc1d20 has been classified as Red List (Low Evidence).
Brain Calcification v1.58 TBC1D20 Zornitza Stark reviewed gene: TBC1D20: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Warburg micro syndrome 4, MIM# 615663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.58 STN1 Zornitza Stark Publications for gene: STN1 were set to 27432940; 32627942
Brain Calcification v1.57 SNORD118 Zornitza Stark Publications for gene: SNORD118 were set to 27571260
Brain Calcification v1.56 SLC46A1 Zornitza Stark Marked gene: SLC46A1 as ready
Brain Calcification v1.56 SLC46A1 Zornitza Stark Gene: slc46a1 has been classified as Green List (High Evidence).
Brain Calcification v1.56 SLC46A1 Zornitza Stark Classified gene: SLC46A1 as Green List (high evidence)
Brain Calcification v1.56 SLC46A1 Zornitza Stark Gene: slc46a1 has been classified as Green List (High Evidence).
Brain Calcification v1.55 SUOX Yetong Chen gene: SUOX was added
gene: SUOX was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: SUOX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUOX were set to 27289259; 23250141; 24384336
Phenotypes for gene: SUOX were set to Sulfite oxidase deficiency, MIM# 272300
Review for gene: SUOX was set to GREEN
Added comment: PMID 27289259 reports 2 unrelated patients with different homozygous SUOX variants (c.713G > A(p.G238Q*) and c.884G > A (p.G295E)) who had thalami calcifications.
PMID 23250141 reports a patient with homozygous SUOX variant (c.1232-1233 delTG) who had faint calcification in the thalami.
PMID 24384336 reports a patient (patient 2) with homozygous SUOX variant (c.1232-1233delT) who had faint calcification in both thalami.
Sources: Expert list
Mendeliome v1.825 OXGR1 Bryony Thompson Publications for gene: OXGR1 were set to PMID:35671463
Brain Calcification v1.55 TBC1D20 Yetong Chen gene: TBC1D20 was added
gene: TBC1D20 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: TBC1D20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D20 were set to 32740904
Phenotypes for gene: TBC1D20 were set to Cerebroretinal microangiopathy with calcifications and cysts 2, MIM# 617341
Review for gene: TBC1D20 was set to RED
Added comment: Limited evidence supports the causal role of TBC1D20 in brain calcification.
PMID 32740904 reports one patient (case 34) with homozygous TBC1D20 variant (c.199C>T (p.Arg67*)) who developed bilateral faint calcification in basal ganglia.
Sources: Expert list
Brain Calcification v1.55 STN1 Yetong Chen reviewed gene: STN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34110109; Phenotypes: Cerebroretinal microangiopathy with calcifications and cysts 2, MIM# 617341; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.55 SNORD118 Yetong Chen reviewed gene: SNORD118: Rating: GREEN; Mode of pathogenicity: None; Publications: 34220662, 28177126, 34986804; Phenotypes: Leukoencephalopathy, brain calcifications, and cysts, MIM# 614561; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.55 SLC46A1 Yetong Chen gene: SLC46A1 was added
gene: SLC46A1 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: SLC46A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC46A1 were set to 33146883; 28685492; 24534056; 27938595
Phenotypes for gene: SLC46A1 were set to Folate malabsorption, hereditary, MIM# 229050
Review for gene: SLC46A1 was set to GREEN
Added comment: PMID 33146883 reports a patient with homozygous SLC46A1 variant (c.620dupG (p.Y208Lfs *25)) who had calcifications in bilateral basal ganglia, thalamus, and subcortical white matter.
PMID 28685492 reports a patient (case 2) with homozygous SLC46A1 variant (c.198C>A (p.Cys66*)) who developed basal ganglia calcification.
PMID 24534056 reports a patient with compound heterozygous SLC46A1 variants (c.1A>T (MIL) and c.194-195insG (p.Cys66LeufsX99)) who developed calcifications in bilateral frontal, temporal, parietal and occipital lobes, and basal ganglia.
PMID 27938595 reports 2 patients harbouring SLC46A1 variants who had progressive bilateral symmetrical calcification. Both patients had compound heterozygous variants. Patient 1 had c. 1238T>C (L413P) and c. 194-195insG (p.Cys66LeufsX99) while patient 2 had c. 1A>T (M1L) and c. 194-195insG (p.Cys66LeufsX99). It should be noted that this publication is written in Chinese and only the abstract is available in English, so details about the calcifications are not available.
Sources: Expert list
Mendeliome v1.824 KPNA7 Zornitza Stark Phenotypes for gene: KPNA7 were changed from Epilepsy; intellectual disability to Oocyte/zygote/embryo maturation arrest 17, MIM# 620319; Neurodevelopmental disorder
Mendeliome v1.823 KPNA7 Zornitza Stark Publications for gene: KPNA7 were set to 24045845; 32179771
Mendeliome v1.822 KPNA7 Zornitza Stark Classified gene: KPNA7 as Amber List (moderate evidence)
Mendeliome v1.822 KPNA7 Zornitza Stark Gene: kpna7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.821 KPNA7 Zornitza Stark reviewed gene: KPNA7: Rating: AMBER; Mode of pathogenicity: None; Publications: 36647821; Phenotypes: Oocyte/zygote/embryo maturation arrest 17, MIM# 620319; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Diarrhoea v1.13 ACSL5 Zornitza Stark Marked gene: ACSL5 as ready
Congenital Diarrhoea v1.13 ACSL5 Zornitza Stark Gene: acsl5 has been classified as Red List (Low Evidence).
Congenital Diarrhoea v1.13 ACSL5 Zornitza Stark gene: ACSL5 was added
gene: ACSL5 was added to Congenital Diarrhoea. Sources: Literature
Mode of inheritance for gene: ACSL5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACSL5 were set to 33191500
Phenotypes for gene: ACSL5 were set to Diarrhoea 13, MIM# 620357
Review for gene: ACSL5 was set to RED
Added comment: 6 individuals of a large consanguineous family presented in the neonatal period with recurrent vomiting and diarrhea, leading to severe FTT. Autozygosity mapping and WES identified homozygous variant (c.1358C>A:p.(Thr453Lys) in ACSL5. Segregated with affected individuals.

Functional in vitro analysis of the ACSL5 variant by immunofluorescence, western blotting and enzyme assay suggested that Thr453Lys is a loss‐of‐function mutation without any remaining activity.

Affected individuals were treated with total parenteral nutrition or medium‐chain triglyceride‐based formula restricted in long‐chain triglycerides. They responded well and follow up suggests that treatment is only required during early life.
Sources: Literature
Fatty Acid Oxidation Defects v1.14 ACSL5 Zornitza Stark Phenotypes for gene: ACSL5 were changed from Diarrhoea 13, MIM# 620357 to Diarrhoea 13, MIM# 620357
Mendeliome v1.821 ACSL5 Zornitza Stark Phenotypes for gene: ACSL5 were changed from severe FTT (no OMIM #) to Diarrhoea 13, MIM# 620357
Fatty Acid Oxidation Defects v1.14 ACSL5 Zornitza Stark Phenotypes for gene: ACSL5 were changed from Diarrhea 13, MIM# 620357 to Diarrhoea 13, MIM# 620357
Fatty Acid Oxidation Defects v1.13 ACSL5 Zornitza Stark Phenotypes for gene: ACSL5 were changed from Diarrhea 13, MIM# 620357 to Diarrhea 13, MIM# 620357
Fatty Acid Oxidation Defects v1.13 ACSL5 Zornitza Stark Phenotypes for gene: ACSL5 were changed from severe FTT (no OMIM #) to Diarrhea 13, MIM# 620357
Polycystic liver disease v1.8 LRP5 Zornitza Stark edited their review of gene: LRP5: Changed publications: 25920554, 24706814
Brain Calcification v1.55 RAB39B Bryony Thompson Marked gene: RAB39B as ready
Brain Calcification v1.55 RAB39B Bryony Thompson Gene: rab39b has been classified as Red List (Low Evidence).
Brain Calcification v1.55 RAB39B Bryony Thompson Classified gene: RAB39B as Red List (low evidence)
Brain Calcification v1.55 RAB39B Bryony Thompson Gene: rab39b has been classified as Red List (Low Evidence).
Brain Calcification v1.54 GJA1 Bryony Thompson Classified gene: GJA1 as Green List (high evidence)
Brain Calcification v1.54 GJA1 Bryony Thompson Added comment: Comment on list classification: Brain calcification appears to be a variable feature of the ODDD phenotype
Brain Calcification v1.54 GJA1 Bryony Thompson Gene: gja1 has been classified as Green List (High Evidence).
Brain Calcification v1.53 GJA1 Bryony Thompson Marked gene: GJA1 as ready
Brain Calcification v1.53 GJA1 Bryony Thompson Gene: gja1 has been classified as Green List (High Evidence).
Brain Calcification v1.53 GJA1 Bryony Thompson Deleted their comment
Brain Calcification v1.53 GJA1 Bryony Thompson Added comment: Comment on mode of inheritance: Brain calcification appears to be a variable feature of the ODDD phenotype
Brain Calcification v1.53 GJA1 Bryony Thompson Mode of inheritance for gene: GJA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Brain Calcification v1.52 GJA1 Bryony Thompson Classified gene: GJA1 as Green List (high evidence)
Brain Calcification v1.52 GJA1 Bryony Thompson Gene: gja1 has been classified as Green List (High Evidence).
Mosaic skin disorders v1.9 PORCN Bryony Thompson Marked gene: PORCN as ready
Mosaic skin disorders v1.9 PORCN Bryony Thompson Gene: porcn has been classified as Green List (High Evidence).
Mosaic skin disorders v1.9 PORCN Bryony Thompson Classified gene: PORCN as Green List (high evidence)
Mosaic skin disorders v1.9 PORCN Bryony Thompson Added comment: Comment on list classification: Added from PanelApp UK mosaic skin disorders panel
Mosaic skin disorders v1.9 PORCN Bryony Thompson Gene: porcn has been classified as Green List (High Evidence).
Mosaic skin disorders v1.8 BRAF Bryony Thompson Classified gene: BRAF as Green List (high evidence)
Mosaic skin disorders v1.8 BRAF Bryony Thompson Added comment: Comment on list classification: Added from PanelApp UK Mosaic skin disorders panel
Mosaic skin disorders v1.8 BRAF Bryony Thompson Gene: braf has been classified as Green List (High Evidence).
Mosaic skin disorders v1.7 BRAF Bryony Thompson Marked gene: BRAF as ready
Mosaic skin disorders v1.7 BRAF Bryony Thompson Gene: braf has been classified as Green List (High Evidence).
Mosaic skin disorders v1.7 BRAF Bryony Thompson Classified gene: BRAF as Green List (high evidence)
Mosaic skin disorders v1.7 BRAF Bryony Thompson Gene: braf has been classified as Green List (High Evidence).
Fetal anomalies v1.104 DNM1 Zornitza Stark Phenotypes for gene: DNM1 were changed from Developmental and epileptic encephalopathy 31, OMIM:616346 to Developmental and epileptic encephalopathy 31A, autosomal dominant, MIM# 616346; Developmental and epileptic encephalopathy 31B, autosomal recessive, MIM# 620352
Fetal anomalies v1.103 DNM1 Zornitza Stark edited their review of gene: DNM1: Changed phenotypes: Developmental and epileptic encephalopathy 31A, autosomal dominant, MIM# 616346, Developmental and epileptic encephalopathy 31B, autosomal recessive, MIM# 620352
Intellectual disability syndromic and non-syndromic v0.5210 DNM1 Zornitza Stark Phenotypes for gene: DNM1 were changed from Developmental and epileptic encephalopathy 31, OMIM:616346 to Developmental and epileptic encephalopathy 31A, autosomal dominant, MIM# 616346; Developmental and epileptic encephalopathy 31B, autosomal recessive, MIM# 620352
Intellectual disability syndromic and non-syndromic v0.5209 DNM1 Zornitza Stark edited their review of gene: DNM1: Changed phenotypes: Developmental and epileptic encephalopathy 31A, autosomal dominant, MIM# 616346, Developmental and epileptic encephalopathy 31B, autosomal recessive, MIM# 620352
Genetic Epilepsy v0.1843 DNM1 Zornitza Stark Marked gene: DNM1 as ready
Genetic Epilepsy v0.1843 DNM1 Zornitza Stark Gene: dnm1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1843 DNM1 Zornitza Stark Phenotypes for gene: DNM1 were changed from Developmental and epileptic encephalopathy 31, OMIM:616346 to Developmental and epileptic encephalopathy 31A, autosomal dominant, MIM# 616346; Developmental and epileptic encephalopathy 31B, autosomal recessive, MIM# 620352
Genetic Epilepsy v0.1842 DNM1 Zornitza Stark edited their review of gene: DNM1: Changed phenotypes: Developmental and epileptic encephalopathy 31A, autosomal dominant, MIM# 616346, Developmental and epileptic encephalopathy 31B, autosomal recessive, MIM# 620352
Mendeliome v1.820 DNM1 Zornitza Stark Phenotypes for gene: DNM1 were changed from Developmental and epileptic encephalopathy 31, OMIM:616346 to Developmental and epileptic encephalopathy 31A, autosomal dominant, MIM# 616346; Developmental and epileptic encephalopathy 31B, autosomal recessive, MIM# 620352
Mendeliome v1.819 DNM1 Zornitza Stark edited their review of gene: DNM1: Changed phenotypes: Developmental and epileptic encephalopathy 31A, autosomal dominant, MIM# 616346, Developmental and epileptic encephalopathy 31B, autosomal recessive, MIM# 620352
Leukodystrophy - adult onset v0.107 PLD3 Bryony Thompson Classified gene: PLD3 as Amber List (moderate evidence)
Leukodystrophy - adult onset v0.107 PLD3 Bryony Thompson Gene: pld3 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.51 SLC20A2 Yetong Chen reviewed gene: SLC20A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28162874, 31267306, 35850697, 34025715; Phenotypes: Basal ganglia calcification, idiopathic, 1, MIM# 213600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy - adult onset v0.106 PLD3 Tegan French gene: PLD3 was added
gene: PLD3 was added to Leukodystrophy - adult onset. Sources: Literature
Mode of inheritance for gene: PLD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLD3 were set to PMID: 34267643
Phenotypes for gene: PLD3 were set to Leukodystrophy
Review for gene: PLD3 was set to AMBER
Added comment: Unconfirmed gene-disease association for biallelic LOF variants in PLD3 and leukodystrophy.
- Single patient in literature with homozygous frameshift nonsense variants in PLD3. This patient had leukodystrophy, vision and hearing impairment, impaired kidney function.
- Homozygous frameshift nonsense variants in another unpublished patient with leukodystrophy
Sources: Literature
Brain Calcification v1.51 SAMHD1 Yetong Chen reviewed gene: SAMHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35418820, 36405817; Phenotypes: Aicardi-Goutieres syndrome 5, MIM# 612952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.51 RNASEH2C Yetong Chen reviewed gene: RNASEH2C: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301648, 33681774, 27411419; Phenotypes: Aicardi-Goutieres syndrome 3, MIM# 610329; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.51 RNASEH2B Yetong Chen reviewed gene: RNASEH2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301648, 33482855, 30826161, 26581299; Phenotypes: Aicardi-Goutieres syndrome 2, MIM# 610181; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic Atrophy v1.12 SPG7 Elena Savva reviewed gene: SPG7: Rating: GREEN; Mode of pathogenicity: None; Publications: 32548275, 36367250, 35243150; Phenotypes: Optical atrophy MONDO#0003608); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.5209 RBSN Elena Savva commented on gene: RBSN
Mendeliome v1.819 INTS11 Achchuthan Shanmugasundram edited their review of gene: INTS11: Changed phenotypes: intellectual disability, MONDO:0001071
Mendeliome v1.819 INTS11 Achchuthan Shanmugasundram gene: INTS11 was added
gene: INTS11 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: INTS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS11 were set to 37054711
Review for gene: INTS11 was set to GREEN
Added comment: Comment on gene rating: This gene should be rated GREEN in Intellectual disability panel as it has 10 unrelated cases and functional evidence in support of this association.

PMID:37054711 reported ten unrelated families with biallelic variants in INTS11 gene and they present with intellectual disability, global developmental and language delay, impaired motor development, and brain atrophy.

Functional studies in Drosophila showed that dIntS11 (fly ortholog of INTS11) is essential and expressed in the central nervous systems in a subset of neurons and most glia in larval and adult stages. In addition, genes with two variants (p.Arg17Leu and p.His414Tyr) fail to rescue the lethality of null mutants in the Drosophila model, indicating that they are strong loss-of-function variants. The other five variants (p.Gly55Ser, p.Leu138Phe, p.Lys396Glu, p.Val517Met and p.Ile553Glu) rescue lethality but cause a shortened lifespan and bang sensitivity and affect locomotor activity, indicating that they are partial loss-of-function variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5209 DNAH14 Zornitza Stark Tag disputed tag was added to gene: DNAH14.
Genetic Epilepsy v0.1842 DNAH14 Zornitza Stark Tag disputed tag was added to gene: DNAH14.
Mendeliome v1.819 DNAH14 Zornitza Stark Tag disputed tag was added to gene: DNAH14.
Intellectual disability syndromic and non-syndromic v0.5209 DNAH14 Elena Savva Classified gene: DNAH14 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5209 DNAH14 Elena Savva Gene: dnah14 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5209 DNAH14 Elena Savva Classified gene: DNAH14 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5209 DNAH14 Elena Savva Gene: dnah14 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5208 DNAH14 Elena Savva reviewed gene: DNAH14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1842 DNAH14 Elena Savva Classified gene: DNAH14 as Red List (low evidence)
Genetic Epilepsy v0.1842 DNAH14 Elena Savva Gene: dnah14 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1842 DNAH14 Elena Savva Classified gene: DNAH14 as Red List (low evidence)
Genetic Epilepsy v0.1842 DNAH14 Elena Savva Gene: dnah14 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1841 DNAH14 Elena Savva reviewed gene: DNAH14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.819 DNAH14 Elena Savva commented on gene: DNAH14
Mendeliome v1.819 DNAH14 Elena Savva Classified gene: DNAH14 as Red List (low evidence)
Mendeliome v1.819 DNAH14 Elena Savva Gene: dnah14 has been classified as Red List (Low Evidence).
Brain Calcification v1.51 MT-ATP6 Yetong Chen edited their review of gene: MT-ATP6: Changed phenotypes: Leigh syndrome, MIM* 516060
Brain Calcification v1.51 QDPR Yetong Chen changed review comment from: There is insufficient evidence supporting the causal role of the QDPR gene in brain calcification.
Sources: Expert list; to: There is insufficient evidence supporting the causal role of the QDPR gene in brain calcification.
The suggested literature (PMID 2135679) is not accessible in PubMed. A similar paper, PMID 2785251, reports intracranial calcification in a patient with dihydropteridine reductase deficiency. DNA sequencing was not available when the case was reported.
Sources: Expert list
Brain Calcification v1.51 QDPR Yetong Chen gene: QDPR was added
gene: QDPR was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: QDPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: QDPR were set to 2135679
Phenotypes for gene: QDPR were set to Dihydropteridine Reductase (DHPR) Deficiency, MIM* 612676
Review for gene: QDPR was set to RED
Added comment: There is insufficient evidence supporting the causal role of the QDPR gene in brain calcification.
Sources: Expert list
Brain Calcification v1.51 RAB39B Yetong Chen gene: RAB39B was added
gene: RAB39B was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: RAB39B was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RAB39B were set to 27943471
Phenotypes for gene: RAB39B were set to Intellectual developmental disorder, X-linked 72, MIM# 300271
Review for gene: RAB39B was set to RED
Added comment: Only one 2 cases from the same family are reported, insufficient evidence supports the causal role of the RAB39B gene in brain calcification.
PMID 27943471 reports 2 patients (II-2 and III-1) from the same family harbouring a RAB39B variant (c.536dupA, p.E179fsX48) who developed brain calcification.
Sources: Expert list
Brain Calcification v1.51 PTS Yetong Chen gene: PTS was added
gene: PTS was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: PTS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTS were set to 16601879; 32734340
Phenotypes for gene: PTS were set to Hyperphenylalaninemia, BH4-deficient, A, MIM# 261640
Review for gene: PTS was set to RED
Added comment: Although brain calcification might be seen in patients with BH4 deficiency, none of the papers mentions PTS variants found in the affected patients.
Further, there are multiple genes that can cause BH4 deficiency, of which PTS is one of them.
The suggested literature, PMID 16601879, reports a BH4 deficiency patient with brain calcification (No.544). However, the mutation analysis was not done for this patient.
Insufficient evidence suggests the causal role of the PTS gene in brain calcification.
Sources: Expert list
Brain Calcification v1.51 PTH Yetong Chen gene: PTH was added
gene: PTH was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: PTH was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PTH were set to 29383229
Phenotypes for gene: PTH were set to Hypoparathyroidism, familial isolated 1, MIM# 146200
Review for gene: PTH was set to RED
Added comment: Several publications report brain calcifications found in patients with hyperparathyroidism (e.g. PMID 29383229); however, none of them reports the genetic profiles of the patients.
In addition, less than 10% of hyperparathyroidism cases are due to genetic causes.
Thus, limited evidence suggests a causal role of the PTH gene in brain calcification.
Sources: Expert list
Brain Calcification v1.51 PSMB8 Yetong Chen gene: PSMB8 was added
gene: PSMB8 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: PSMB8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB8 were set to 28895430; 23768303
Phenotypes for gene: PSMB8 were set to Proteasome-associated autoinflammatory syndrome 1 and digenic forms, MIM# 256040
Review for gene: PSMB8 was set to RED
Added comment: Insufficient evidence supports the causal role of the PSMB8 gene in brain calcification.
PMID 28895430 report a patient with homozygous PSMB8 variants (p.A92T) who developed basal ganglia calcification.
PMID 23768303 reports a patient with heterozygous PSMB8 variants (p.A92T/p.T75M) who had brain calcification.
Sources: Expert list
Brain Calcification v1.51 PSMG2 Yetong Chen gene: PSMG2 was added
gene: PSMG2 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: PSMG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMG2 were set to 30664889
Phenotypes for gene: PSMG2 were set to Proteasome-associated autoinflammatory syndrome 4, MIM# 619183
Review for gene: PSMG2 was set to RED
Added comment: There is limited evidence supporting the causal role of PSMG2 in brain calcification.
PMID 30664889 reports a patient with heterozygous PSMG2 variants (c.666_667delGT, p.Y223Sfs*2 and c.675 T>G, p.N225K) who had bilateral basal ganglia calcifications.
Sources: Expert list
Brain Calcification v1.51 PLXNA1 Yetong Chen gene: PLXNA1 was added
gene: PLXNA1 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: PLXNA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PLXNA1 were set to 34054129
Phenotypes for gene: PLXNA1 were set to Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955
Review for gene: PLXNA1 was set to RED
Added comment: There is limited evidence supporting the causal role of the PLXNA1 gene in brain calcification.
PMID 34054129 reports a patient (H:II-1) with a PLXNA1 variant (c.5242C>T) who developed basal ganglia calcifications.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5208 RFX7 Zornitza Stark Phenotypes for gene: RFX7 were changed from ID, ASD, ADHD to Intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities, MIM# 620330
Mendeliome v1.818 RFX7 Zornitza Stark Phenotypes for gene: RFX7 were changed from ID, ASD, ADHD to Intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities, MIM# 620330
Mendeliome v1.817 RFX7 Zornitza Stark edited their review of gene: RFX7: Changed phenotypes: Intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities, MIM# 620330
Intellectual disability syndromic and non-syndromic v0.5207 MED11 Zornitza Stark Phenotypes for gene: MED11 were changed from neurodevelopmental disorder MONDO#0700092, MED11-related to Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, MIM# 620327
Intellectual disability syndromic and non-syndromic v0.5206 MED11 Zornitza Stark reviewed gene: MED11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, MIM# 620327; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.103 MED11 Zornitza Stark Phenotypes for gene: MED11 were changed from neurodevelopmental disorder MONDO#0700092, MED11-related to Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, MIM# 620327
Genetic Epilepsy v0.1841 MED11 Zornitza Stark Phenotypes for gene: MED11 were changed from neurodevelopmental disorder MONDO#0700092, MED11-related to Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, MIM# 620327
Genetic Epilepsy v0.1840 MED11 Zornitza Stark reviewed gene: MED11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, MIM# 620327; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.817 MED11 Zornitza Stark Phenotypes for gene: MED11 were changed from neurodevelopmental disorder MONDO#0700092, MED11-related to Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, MIM# 620327
Mendeliome v1.816 MED11 Zornitza Stark reviewed gene: MED11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, MIM# 620327; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.398 MED11 Zornitza Stark Phenotypes for gene: MED11 were changed from neurodevelopmental disorder MONDO#0700092, MED11-related to Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, MIM# 620327
Arthrogryposis v0.397 MED11 Zornitza Stark reviewed gene: MED11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, MIM# 620327; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.816 MARS Zornitza Stark Phenotypes for gene: MARS were changed from Interstitial lung and liver disease, MIM#615486; Charcot-Marie-Tooth disease, axonal, type 2U, MIM# 616280; Trichothiodystrophy 9, nonphotosensitive, MIM# 619692 to Interstitial lung and liver disease, MIM#615486; Charcot-Marie-Tooth disease, axonal, type 2U, MIM# 616280; Trichothiodystrophy 9, nonphotosensitive, MIM# 619692; Spastic paraplegia 70, autosomal recessive, MIM# 620323
Mendeliome v1.815 MARS Zornitza Stark Publications for gene: MARS were set to 23729695; 24354524; 29655802; 24103465; 25913036; 33909043
Mendeliome v1.814 MARS Zornitza Stark edited their review of gene: MARS: Added comment: Six individuals from two unrelated families reported with SPG.; Changed publications: 23729695, 24354524, 29655802, 24103465, 25913036, 24482476, 34585293; Changed phenotypes: Interstitial lung and liver disease, MIM#615486, Charcot-Marie-Tooth disease, axonal, type 2U, MIM# 616280, Spastic paraplegia 70, autosomal recessive, MIM# 620323
Hereditary Spastic Paraplegia - paediatric v1.61 MARS Zornitza Stark Phenotypes for gene: MARS were changed from Complicated hereditary spastic paraplegia; Charcot-Marie-Tooth disease, axonal, type 2U, MIM# 616280 to Spastic paraplegia 70, autosomal recessive, MIM# 620323
Hereditary Spastic Paraplegia - paediatric v1.60 MARS Zornitza Stark Publications for gene: MARS were set to 24482476
Hereditary Spastic Paraplegia - paediatric v1.59 MARS Zornitza Stark Classified gene: MARS as Amber List (moderate evidence)
Hereditary Spastic Paraplegia - paediatric v1.59 MARS Zornitza Stark Gene: mars has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia - paediatric v1.58 MARS Zornitza Stark reviewed gene: MARS: Rating: AMBER; Mode of pathogenicity: None; Publications: 34585293; Phenotypes: Spastic paraplegia 70, autosomal recessive, MIM# 620323; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.286 WARS Zornitza Stark Phenotypes for gene: WARS were changed from Neurodevelopmental disorder (MONDO:0700092), WARS-related to Neurodevelopmental disorder withmicrocephaly and speech delay, with or without brain abnormalities,MIM# 620317
Leukodystrophy - paediatric v0.285 WARS Zornitza Stark reviewed gene: WARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder withmicrocephaly and speech delay, with or without brain abnormalities,MIM# 620317; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5206 WARS Zornitza Stark Phenotypes for gene: WARS were changed from Neurodevelopmental disorder (MONDO:0700092), WARS-related to Neurodevelopmental disorder withmicrocephaly and speech delay, with or without brain abnormalities,MIM# 620317
Intellectual disability syndromic and non-syndromic v0.5205 WARS Zornitza Stark reviewed gene: WARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder withmicrocephaly and speech delay, with or without brain abnormalities,MIM# 620317; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.203 WARS Zornitza Stark Phenotypes for gene: WARS were changed from Neurodevelopmental disorder (MONDO:0700092), WARS-related to Neurodevelopmental disorder withmicrocephaly and speech delay, with or without brain abnormalities,MIM# 620317
Microcephaly v1.202 WARS Zornitza Stark reviewed gene: WARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder withmicrocephaly and speech delay, with or without brain abnormalities,MIM# 620317; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.814 WARS Zornitza Stark Phenotypes for gene: WARS were changed from Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); Neurodevelopmental disorder (MONDO:0700092), WARS-related to Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); Neurodevelopmental disorder withmicrocephaly and speech delay, with or without brain abnormalities, MIM# 620317
Cone-rod Dystrophy v0.50 UNC119 Zornitza Stark Phenotypes for gene: UNC119 were changed from Cone-rod dystrophy, MONDO:0015993 to Cone-rod dystrophy 24, MIM# 620342
Cone-rod Dystrophy v0.49 UNC119 Zornitza Stark reviewed gene: UNC119: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cone-rod dystrophy 24, MIM# 620342; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.813 UNC119 Zornitza Stark Phenotypes for gene: UNC119 were changed from Cone-rod dystrophy, MONDO:0015993; Immunodeficiency 13 MIM#615518 to Cone-rod dystrophy 24, MIM# 620342; Immunodeficiency 13 MIM#615518
Mendeliome v1.812 UNC119 Zornitza Stark edited their review of gene: UNC119: Changed phenotypes: Cone-rod dystrophy 24, MIM# 620342, Immunodeficiency 13 MIM#615518
Brain Calcification v1.51 PDGFRB Yetong Chen reviewed gene: PDGFRB: Rating: ; Mode of pathogenicity: None; Publications: 29955172, 23255827; Phenotypes: Basal ganglia calcification, idiopathic, 4, MIM# 615007; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v1.51 PDGFB Yetong Chen reviewed gene: PDGFB: Rating: GREEN; Mode of pathogenicity: None; Publications: 27433546, 35747618, 25211641, 29955172, 31267306, 28162874; Phenotypes: Basal ganglia calcification, idiopathic, 5, MIM# 615483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v1.51 PCDH12 Yetong Chen gene: PCDH12 was added
gene: PCDH12 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: PCDH12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDH12 were set to 28804758; 34773825; 30178464
Phenotypes for gene: PCDH12 were set to Diencephalic-mesencephalic junction dysplasia syndrome 1, MIM# 251280
Review for gene: PCDH12 was set to GREEN
Added comment: PMID 28804758 reports a patient with a homozygous PCDH12 nonsense variant who developed brain calcification. The authors also screen the PCDH12 gene in 79 patients with unknown causes of brain calcification and detected 4 rare PCDH12 variants in 4 unrelated patients. This finding confirms the association between PCDH12 and brain calcification, supported by very low frequencies in the ExAC database, functional studies of the variants, studies of patient cells, and segregation studies.
PMID 34773825 reports a patient with a homozygous truncating variant (c.1176G>A; p.Trp392*) in PCDH12 who developed brain calcification.
PMID 30178464 described 14 affected individuals from 8 families who carried PCDH12 variants. The authors report 6 patients with PCDH12 variants who developed subtle brain calcifications; however, the relationship between these patients is unclear and the results of CT studies of these 6 patients are not shown in the article.
Sources: Expert list
Brain Calcification v1.51 PANK2 Yetong Chen gene: PANK2 was added
gene: PANK2 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: PANK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PANK2 were set to 23968566; 29642163; 28024710
Phenotypes for gene: PANK2 were set to Neurodegeneration with brain iron accumulation 1, MIM# 234200
Review for gene: PANK2 was set to RED
Added comment: The 3 cases were reported within 5 years (2013-2018); however, no more new cases are reported after 2018. Hence, limited evidence supports the causal role of the MOCS1 gene in brain calcification.
PMID 23968566 reports a patient with heterozygous PANK2 variants (p.G521R and p.T528M) who exhibited basal ganglia calcifications.
PMID 29642163 reports a patient with heterozygous PANK2 variants (p.D217G and p.D447E) who developed basal ganglia calcifications.
PMID 28024710 reports a patient with 2 homozygous PANK2 variants (p.Asp403Val) who developed bilateral calcification of globus pallidus.
Sources: Expert list
Brain Calcification v1.51 MT-ATP6 Yetong Chen gene: MT-ATP6 was added
gene: MT-ATP6 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene gene: MT-ATP6 was set to MITOCHONDRIAL
Publications for gene: MT-ATP6 were set to 32042910; 29929013
Phenotypes for gene: MT-ATP6 were set to Leigh syndrome, MIM# 256000
Review for gene: MT-ATP6 was set to RED
Added comment: Limited evidence supports the causal role of the MT-ATP6 gene in brain calcification.
PMID 32042910 reports a patient (patient P2) with the m.8782G>A: p.(Gly86*) variant in MT-ATP6 who developed basal ganglia calcification.
PMID PMID: 29929013 reports a patient with the m.8936T > A variant in MT-ATP6 who developed brain calcification.
Sources: Expert list
Brain Calcification v1.51 MOCS1 Yetong Chen gene: MOCS1 was added
gene: MOCS1 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: MOCS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOCS1 were set to 27289259
Phenotypes for gene: MOCS1 were set to Molybdenum cofactor deficiency A, MIM# 252150
Review for gene: MOCS1 was set to RED
Added comment: Limited evidence supports the causal role of the MOCS1 gene in brain calcification.
PMID reports 2 patients (patients 1 and 5) with different homozygous MOCS1 variants (c.253C > T (p.Q85*) and c.722_722delT (p.L241Rfs*6)) who developed brain calcification.
Sources: Expert list
Brain Calcification v1.51 JAM2 Yetong Chen reviewed gene: JAM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32142645; Phenotypes: Basal ganglia calcification, idiopathic, 8, autosomal recessive, MIM# 618824; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.51 ISG15 Yetong Chen gene: ISG15 was added
gene: ISG15 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: ISG15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ISG15 were set to 25307056; 32944031
Phenotypes for gene: ISG15 were set to Immunodeficiency 38 with BG calcification, MIM# 616126
Review for gene: ISG15 was set to GREEN
Added comment: Brain calcification is consistently observed in patients with biallelic pathogenic variants in ISG15.
PMID 25307056 reports 5 patients (patients P1-3, P5 and P6) from 3 unrelated families who had ISG15 variants and developed brain calcification. In this paper, patient P4 was from the same family as patients P5 and P6; however, P4 only had inferred genotype so she is not counted here.
PMID 32944031 reports a patient with compound heterozygous ISG15 variants who developed brain calcification.
Sources: Expert list
Mendeliome v1.812 DNAJB4 Zornitza Stark Phenotypes for gene: DNAJB4 were changed from Congenital myopathy 21 with early respiratory failure, MIM# 620326 to Congenital myopathy 21 with early respiratory failure, MIM# 620326; distal myopathy MONDO:0018949
Mendeliome v1.811 DNAJB4 Zornitza Stark Publications for gene: DNAJB4 were set to PMID: 36264506
Mendeliome v1.810 DNAJB4 Zornitza Stark Mode of inheritance for gene: DNAJB4 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.809 DNAJB4 Zornitza Stark Phenotypes for gene: DNAJB4 were changed from Myopathy, MONDO:0005336, DNAJB4-related to Congenital myopathy 21 with early respiratory failure, MIM# 620326
Mendeliome v1.808 DNAJB4 Zornitza Stark reviewed gene: DNAJB4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital myopathy 21 with early respiratory failure, MIM# 620326; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.51 IFIH1 Yetong Chen reviewed gene: IFIH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301648, 31898846, 29782060; Phenotypes: Aicardi-Goutieres syndrome 7, MIM# 615846; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.230 VAPB Sangavi Sivagnanasundram reviewed gene: VAPB: Rating: AMBER; Mode of pathogenicity: None; Publications: 18322265, 15372378, 23771029; Phenotypes: Amyotrophic lateral sclerosis 8 (MONDO:0012077, MIM 608627); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Incidentalome v0.230 VCP Sangavi Sivagnanasundram reviewed gene: VCP: Rating: GREEN; Mode of pathogenicity: None; Publications: 21145000, 33004675; Phenotypes: Frontotemporal dementia and/or Amyotrophic lateral sclerosis 6 (MONDO:0013501, MIM 613954), Inclusion body myopathy with early-onset Paget Disease and FTD [IBMPFD] (MONDO:0000507MIM 167320); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.145 POMGNT1 Bryony Thompson Marked gene: POMGNT1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.145 POMGNT1 Bryony Thompson Gene: pomgnt1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.145 POMGNT1 Bryony Thompson Phenotypes for gene: POMGNT1 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type to Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8 MIM#618135
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.144 POMGNT1 Bryony Thompson Publications for gene: POMGNT1 were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.143 PLEC Bryony Thompson Marked gene: PLEC as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.143 PLEC Bryony Thompson Gene: plec has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.143 PLEC Bryony Thompson Publications for gene: PLEC were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.142 LAMA2 Bryony Thompson Marked gene: LAMA2 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.142 LAMA2 Bryony Thompson Gene: lama2 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.142 LAMA2 Bryony Thompson Phenotypes for gene: LAMA2 were changed from Muscular dystrophy, congenital, merosin deficient or partially deficient, 607855 to Muscular dystrophy, congenital, merosin deficient or partially deficient, MIM# 607855; Muscular dystrophy, limb-girdle, autosomal recessive 23, MIM# 618138
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.141 LAMA2 Bryony Thompson Publications for gene: LAMA2 were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.140 GMPPB Bryony Thompson Phenotypes for gene: GMPPB were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 615352
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.139 FKTN Bryony Thompson Marked gene: FKTN as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.139 FKTN Bryony Thompson Gene: fktn has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.139 FKTN Bryony Thompson Publications for gene: FKTN were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.138 FKRP Bryony Thompson Marked gene: FKRP as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.138 FKRP Bryony Thompson Gene: fkrp has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.138 FKRP Bryony Thompson Publications for gene: FKRP were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.137 FHL1 Bryony Thompson Marked gene: FHL1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.137 FHL1 Bryony Thompson Gene: fhl1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.137 FHL1 Bryony Thompson Phenotypes for gene: FHL1 were changed from Emery-Dreifuss muscular dystrophy to Reducing body myopathy MONDO:0019948; X-linked Emery-Dreifuss muscular dystrophy MONDO:0010680
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.136 FHL1 Bryony Thompson Publications for gene: FHL1 were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.135 EMD Bryony Thompson Marked gene: EMD as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.135 EMD Bryony Thompson Gene: emd has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.135 EMD Bryony Thompson Publications for gene: EMD were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.134 DPM3 Bryony Thompson Marked gene: DPM3 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.134 DPM3 Bryony Thompson Gene: dpm3 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.134 DOK7 Bryony Thompson Marked gene: DOK7 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.134 DOK7 Bryony Thompson Gene: dok7 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.134 DOK7 Bryony Thompson Publications for gene: DOK7 were set to PMID: 31453852; 32360404
Motor Neurone Disease v0.138 GLT8D1 Sarah Leigh reviewed gene: GLT8D1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30811981, 35525134:33581933:31653410:33714647:34746377; Phenotypes: familial amyotrophic lateral sclerosis, MONDO:0005144; Mode of inheritance: None
Eye Anterior Segment Abnormalities v1.5 ASPH Chirag Patel Classified gene: ASPH as Green List (high evidence)
Eye Anterior Segment Abnormalities v1.5 ASPH Chirag Patel Gene: asph has been classified as Green List (High Evidence).
Eye Anterior Segment Abnormalities v1.4 ASPH Chirag Patel gene: ASPH was added
gene: ASPH was added to Eye Anterior Segment Abnormalities. Sources: Literature
Mode of inheritance for gene: ASPH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASPH were set to PMID: 24768550, 30194805, 34018898, 35918038
Phenotypes for gene: ASPH were set to Traboulsi syndrome , MIM#601552
Added comment: Traboulsi syndrome, otherwise known as facial dysmorphism, lens dislocation, anterior-segment abnormalities and spontaneous filtering blebs, is an autosomal recessive condition associated with characteristic ocular features including dislocated crystalline lenses, anterior segment abnormalities and in some individuals, non-traumatic conjunctival cysts. There is a distinctive facial appearance which includes flattened malar region with convex nasal ridge. Alterations in the aspartate beta-hydroxylase (ASPH) gene are known to be the cause of the condition. Numerous families reported.
Sources: Literature
Multiple pterygium syndrome_Fetal akinesia sequence v1.3 KIF21A Chirag Patel Classified gene: KIF21A as Amber List (moderate evidence)
Multiple pterygium syndrome_Fetal akinesia sequence v1.3 KIF21A Chirag Patel Gene: kif21a has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.397 KIF21A Chirag Patel Classified gene: KIF21A as Amber List (moderate evidence)
Arthrogryposis v0.397 KIF21A Chirag Patel Gene: kif21a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.102 KIF21A Chirag Patel Classified gene: KIF21A as Amber List (moderate evidence)
Fetal anomalies v1.102 KIF21A Chirag Patel Gene: kif21a has been classified as Amber List (Moderate Evidence).
Multiple pterygium syndrome_Fetal akinesia sequence v1.2 KIF21A Chirag Patel gene: KIF21A was added
gene: KIF21A was added to Multiple pterygium syndrome_Fetal akinesia sequence. Sources: Literature
Mode of inheritance for gene: KIF21A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF21A were set to PMID: 34740919
Phenotypes for gene: KIF21A were set to Severe fetal akinesia with arthrogryposis multiplex
Review for gene: KIF21A was set to AMBER
Added comment: 2 unrelated consanguineous Turkish families with 5 affected fetuses with severe fetal akinesia with arthrogryposis multiplex. WES identified different homozygous LOF variants in KIF21A gene (p.Leu449* and p.Arg791Glufs*8). Parents and a healthy sibling were heterozygous carriers. No functional studies.
Sources: Literature
Arthrogryposis v0.396 KIF21A Chirag Patel gene: KIF21A was added
gene: KIF21A was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: KIF21A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF21A were set to PMID: 34740919
Phenotypes for gene: KIF21A were set to Severe fetal akinesia with arthrogryposis multiplex
Review for gene: KIF21A was set to AMBER
Added comment: 2 unrelated consanguineous Turkish families with 5 affected fetuses with severe fetal akinesia with arthrogryposis multiplex. WES identified different homozygous LOF variants in KIF21A gene (p.Leu449* and p.Arg791Glufs*8). Parents and a healthy sibling were heterozygous carriers. No functional studies.
Sources: Literature
Fetal anomalies v1.101 KIF21A Chirag Patel gene: KIF21A was added
gene: KIF21A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KIF21A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF21A were set to PMID: 34740919
Phenotypes for gene: KIF21A were set to Severe fetal akinesia with arthrogryposis multiplex
Review for gene: KIF21A was set to AMBER
Added comment: 2 unrelated consanguineous Turkish families with 5 affected fetuses with severe fetal akinesia with arthrogryposis multiplex. WES identified different homozygous LOF variants in KIF21A gene (p.Leu449* and p.Arg791Glufs*8). Parents and a healthy sibling were heterozygous carriers. No functional studies.
Sources: Literature
Anophthalmia_Microphthalmia_Coloboma v1.32 WNT7B Chirag Patel Classified gene: WNT7B as Green List (high evidence)
Anophthalmia_Microphthalmia_Coloboma v1.32 WNT7B Chirag Patel Gene: wnt7b has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.31 WNT7B Chirag Patel reviewed gene: WNT7B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35790350; Phenotypes: Pulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia and Cardiac defects syndrome, Multiple congenital anomalies/dysmorphic features syndrome MONDO:0043005, WNT7B-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.808 C16orf62 Chirag Patel Classified gene: C16orf62 as Green List (high evidence)
Mendeliome v1.808 C16orf62 Chirag Patel Gene: c16orf62 has been classified as Green List (High Evidence).
Mendeliome v1.808 C16orf62 Chirag Patel Classified gene: C16orf62 as Green List (high evidence)
Mendeliome v1.808 C16orf62 Chirag Patel Gene: c16orf62 has been classified as Green List (High Evidence).
Mendeliome v1.807 C16orf62 Chirag Patel reviewed gene: C16orf62: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36113987; Phenotypes: Ritscher-Schinzel syndrome-3 (RTSC3), MIM#619135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5205 C16orf62 Chirag Patel Classified gene: C16orf62 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5205 C16orf62 Chirag Patel Gene: c16orf62 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5204 C16orf62 Chirag Patel reviewed gene: C16orf62: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36113987; Phenotypes: Ritscher-Schinzel syndrome-3 (RTSC3), MIM#619135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.100 C16orf62 Chirag Patel Classified gene: C16orf62 as Green List (high evidence)
Fetal anomalies v1.100 C16orf62 Chirag Patel Gene: c16orf62 has been classified as Green List (High Evidence).
Fetal anomalies v1.99 C16orf62 Chirag Patel reviewed gene: C16orf62: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36113987; Phenotypes: Ritscher-Schinzel syndrome-3 (RTSC3), MIM#619135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.51 GNAS Yetong Chen gene: GNAS was added
gene: GNAS was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: GNAS was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: GNAS were set to 28296742; 35600030; 20444925
Phenotypes for gene: GNAS were set to Pseudohypoparathyroidism Ib, MIM# 603233
Review for gene: GNAS was set to GREEN
Added comment: The imprinting of GNAS is complex. While GNAS is primarily expressed from the maternal allele, only the paternal allele is expressed in some tissues.
Although the number of cases is limited, patients are reported by different authors across the years.
PMID 28296742 reports 2 patients from the same family, who had the same GNAS variant (p.P115S, p.V340M), and developed brain calcification.
PMID 35600030 reports a patient with a rare GNAS variant who developed bilateral basal ganglia calcification.
PMID 20444925 reports 2 patients from the same family who developed brain calcification. The patients had broad epigenetic defects at the GNAS gene and a deletion that exclusively affects exons encoding the antisense transcript (delAS3-4). The deletion is suspected to partially influence the imprinting of some GNAS loci.
Sources: Expert list
Brain Calcification v1.51 GNA11 Yetong Chen gene: GNA11 was added
gene: GNA11 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: GNA11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNA11 were set to 27334330
Phenotypes for gene: GNA11 were set to Hypocalcemia, autosomal dominant 2, MIM# 615361
Review for gene: GNA11 was set to RED
Added comment: PMID 27334330 reports 4 patients with the same GNA11 variant (c.1018G>A), who are from the same family, developed intracranial calcifications.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.132 ANXA11 Bryony Thompson Marked gene: ANXA11 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.132 ANXA11 Bryony Thompson Gene: anxa11 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.132 ANXA11 Bryony Thompson Classified gene: ANXA11 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.132 ANXA11 Bryony Thompson Gene: anxa11 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.131 BICD2 Bryony Thompson Marked gene: BICD2 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.131 BICD2 Bryony Thompson Gene: bicd2 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.131 BICD2 Bryony Thompson Classified gene: BICD2 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.131 BICD2 Bryony Thompson Gene: bicd2 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.130 GFPT1 Bryony Thompson Marked gene: GFPT1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.130 GFPT1 Bryony Thompson Gene: gfpt1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.130 GFPT1 Bryony Thompson Classified gene: GFPT1 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.130 GFPT1 Bryony Thompson Gene: gfpt1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.129 HNRNPA1 Bryony Thompson Marked gene: HNRNPA1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.129 HNRNPA1 Bryony Thompson Gene: hnrnpa1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.129 HNRNPA1 Bryony Thompson Classified gene: HNRNPA1 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.129 HNRNPA1 Bryony Thompson Gene: hnrnpa1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.128 HNRNPA2B1 Bryony Thompson Marked gene: HNRNPA2B1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.128 HNRNPA2B1 Bryony Thompson Gene: hnrnpa2b1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.128 HNRNPA2B1 Bryony Thompson Classified gene: HNRNPA2B1 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.128 HNRNPA2B1 Bryony Thompson Gene: hnrnpa2b1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.127 LDB3 Bryony Thompson Marked gene: LDB3 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.127 LDB3 Bryony Thompson Gene: ldb3 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.127 LDB3 Bryony Thompson Classified gene: LDB3 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.127 LDB3 Bryony Thompson Gene: ldb3 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.126 PABPN1 Bryony Thompson Marked gene: PABPN1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.126 PABPN1 Bryony Thompson Gene: pabpn1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.126 PABPN1 Bryony Thompson Classified gene: PABPN1 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.126 PABPN1 Bryony Thompson Gene: pabpn1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.125 SMPX Bryony Thompson Marked gene: SMPX as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.125 SMPX Bryony Thompson Gene: smpx has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.125 SMPX Bryony Thompson Classified gene: SMPX as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.125 SMPX Bryony Thompson Gene: smpx has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.124 SQSTM1 Bryony Thompson Marked gene: SQSTM1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.124 SQSTM1 Bryony Thompson Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.124 SQSTM1 Bryony Thompson Classified gene: SQSTM1 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.124 SQSTM1 Bryony Thompson Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.123 TIA1 Bryony Thompson Marked gene: TIA1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.123 TIA1 Bryony Thompson Gene: tia1 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.123 TIA1 Bryony Thompson Publications for gene: TIA1 were set to 23401021; 23401021
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.122 TIA1 Bryony Thompson Classified gene: TIA1 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.122 TIA1 Bryony Thompson Gene: tia1 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.121 TMEM43 Bryony Thompson Marked gene: TMEM43 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.121 TMEM43 Bryony Thompson Gene: tmem43 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.121 TMEM43 Bryony Thompson Classified gene: TMEM43 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.121 TMEM43 Bryony Thompson Gene: tmem43 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.120 DMD Bryony Thompson Marked gene: DMD as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.120 DMD Bryony Thompson Gene: dmd has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.120 DMD Bryony Thompson Publications for gene: DMD were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.119 DAG1 Bryony Thompson Marked gene: DAG1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.119 DAG1 Bryony Thompson Gene: dag1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.119 DAG1 Bryony Thompson Publications for gene: DAG1 were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.118 COL6A3 Bryony Thompson Marked gene: COL6A3 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.118 COL6A3 Bryony Thompson Gene: col6a3 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.118 COL6A3 Bryony Thompson Phenotypes for gene: COL6A3 were changed from Bethlem myopathy 1 158810 to Bethlem myopathy 1 MIM#158810; Ullrich congenital muscular dystrophy 1 MIM#254090
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.117 COL6A3 Bryony Thompson Publications for gene: COL6A3 were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.116 COL6A3 Bryony Thompson Mode of inheritance for gene: COL6A3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Severe Combined Immunodeficiency (absent T present B cells) v1.1 POLD3 Peter McNaughton gene: POLD3 was added
gene: POLD3 was added to Severe Combined Immunodeficiency (absent T present B cells). Sources: Literature
Mode of inheritance for gene: POLD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLD3 were set to PMID: 37030525
Phenotypes for gene: POLD3 were set to Severe combined immunodeficiency
Review for gene: POLD3 was set to AMBER
Added comment: Homozygous mutation in POLD3 (NM_006591.3: c.29T>C; p.Ile10Thr) in the offspring of a consanguineous Lebanese family with syndromic T -B +NK- SCID, including neurodevelopmental delay and profound hearing loss.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.115 COL6A2 Bryony Thompson Marked gene: COL6A2 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.115 COL6A2 Bryony Thompson Gene: col6a2 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.115 COL6A2 Bryony Thompson Phenotypes for gene: COL6A2 were changed from Bethlem myopathy 1 158810 to Bethlem myopathy 1 MIM#158810; Ullrich congenital muscular dystrophy 1 MIM#254090
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.114 COL6A2 Bryony Thompson Publications for gene: COL6A2 were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.113 COL6A2 Bryony Thompson Mode of inheritance for gene: COL6A2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.112 COL6A1 Bryony Thompson Marked gene: COL6A1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.112 COL6A1 Bryony Thompson Gene: col6a1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.112 COL6A1 Bryony Thompson Phenotypes for gene: COL6A1 were changed from Bethlem myopathy 1 158810 to Bethlem myopathy MIM#158810; Ullrich congenital muscular dystrophy MIM#254090
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.111 COL6A1 Bryony Thompson Mode of inheritance for gene: COL6A1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.110 COL6A1 Bryony Thompson Publications for gene: COL6A1 were set to
Rhabdomyolysis and Metabolic Myopathy v0.167 DGUOK Bryony Thompson Classified gene: DGUOK as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.167 DGUOK Bryony Thompson Gene: dguok has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.166 DGUOK Bryony Thompson Phenotypes for gene: DGUOK were changed from Rhabdomyolisis; lower limb weakness to Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), MIM# 251880; Portal hypertension, noncirrhotic, 1, MIM# 617068; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4, MIM# 617070
Rhabdomyolysis and Metabolic Myopathy v0.165 DGUOK Bryony Thompson Publications for gene: DGUOK were set to 23043144
Rhabdomyolysis and Metabolic Myopathy v0.164 SUCLA2 Bryony Thompson Publications for gene: SUCLA2 were set to
Rhabdomyolysis and Metabolic Myopathy v0.163 SUCLA2 Bryony Thompson Deleted their review
Rhabdomyolysis and Metabolic Myopathy v0.163 SUCLA2 Bryony Thompson commented on gene: SUCLA2
Rhabdomyolysis and Metabolic Myopathy v0.163 SUCLA2 Bryony Thompson Deleted their review
Rhabdomyolysis and Metabolic Myopathy v0.163 SUCLA2 Bryony Thompson Classified gene: SUCLA2 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.163 SUCLA2 Bryony Thompson Gene: sucla2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.162 SUCLA2 Bryony Thompson Deleted their comment
Rhabdomyolysis and Metabolic Myopathy v0.162 SLC25A20 Bryony Thompson Deleted their review
Rhabdomyolysis and Metabolic Myopathy v0.162 SLC25A20 Bryony Thompson commented on gene: SLC25A20
Rhabdomyolysis and Metabolic Myopathy v0.162 SLC25A20 Bryony Thompson Classified gene: SLC25A20 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.162 SLC25A20 Bryony Thompson Gene: slc25a20 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.161 SLC25A20 Bryony Thompson Deleted their review
Rhabdomyolysis and Metabolic Myopathy v0.161 SLC25A20 Bryony Thompson Deleted their comment
Rhabdomyolysis and Metabolic Myopathy v0.161 PUS1 Bryony Thompson Marked gene: PUS1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.161 PUS1 Bryony Thompson Gene: pus1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.161 PUS1 Bryony Thompson Classified gene: PUS1 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.161 PUS1 Bryony Thompson Gene: pus1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.160 OPA1 Bryony Thompson Marked gene: OPA1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.160 OPA1 Bryony Thompson Gene: opa1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.160 OPA1 Bryony Thompson Classified gene: OPA1 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.160 OPA1 Bryony Thompson Gene: opa1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.159 MGME1 Bryony Thompson Marked gene: MGME1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.159 MGME1 Bryony Thompson Gene: mgme1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.159 MGME1 Bryony Thompson Classified gene: MGME1 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.159 MGME1 Bryony Thompson Gene: mgme1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.158 FLAD1 Bryony Thompson Marked gene: FLAD1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.158 FLAD1 Bryony Thompson Gene: flad1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.158 FLAD1 Bryony Thompson Classified gene: FLAD1 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.158 FLAD1 Bryony Thompson Gene: flad1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.157 SLC22A5 Bryony Thompson Marked gene: SLC22A5 as ready
Rhabdomyolysis and Metabolic Myopathy v0.157 SLC22A5 Bryony Thompson Gene: slc22a5 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.157 SLC22A5 Bryony Thompson Publications for gene: SLC22A5 were set to
Rhabdomyolysis and Metabolic Myopathy v0.156 RYR1 Bryony Thompson Marked gene: RYR1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.156 RYR1 Bryony Thompson Gene: ryr1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.156 RYR1 Bryony Thompson Publications for gene: RYR1 were set to
Rhabdomyolysis and Metabolic Myopathy v0.155 RRM2B Bryony Thompson Marked gene: RRM2B as ready
Rhabdomyolysis and Metabolic Myopathy v0.155 RRM2B Bryony Thompson Gene: rrm2b has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.155 RRM2B Bryony Thompson Publications for gene: RRM2B were set to
Rhabdomyolysis and Metabolic Myopathy v0.154 RBCK1 Bryony Thompson Marked gene: RBCK1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.154 RBCK1 Bryony Thompson Gene: rbck1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.154 RBCK1 Bryony Thompson Publications for gene: RBCK1 were set to
Rhabdomyolysis and Metabolic Myopathy v0.153 PYGM Bryony Thompson Marked gene: PYGM as ready
Rhabdomyolysis and Metabolic Myopathy v0.153 PYGM Bryony Thompson Gene: pygm has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.153 PYGM Bryony Thompson Publications for gene: PYGM were set to
Rhabdomyolysis and Metabolic Myopathy v0.152 POLG2 Bryony Thompson Marked gene: POLG2 as ready
Rhabdomyolysis and Metabolic Myopathy v0.152 POLG2 Bryony Thompson Gene: polg2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.152 POLG2 Bryony Thompson Phenotypes for gene: POLG2 were changed from Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 610131 to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, MIM# 610131
Rhabdomyolysis and Metabolic Myopathy v0.151 POLG2 Bryony Thompson Publications for gene: POLG2 were set to
Rhabdomyolysis and Metabolic Myopathy v0.150 POLG Bryony Thompson Marked gene: POLG as ready
Rhabdomyolysis and Metabolic Myopathy v0.150 POLG Bryony Thompson Gene: polg has been classified as Green List (High Evidence).