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| Fetal anomalies v0.4535 | PPP1CB | Zornitza Stark Phenotypes for gene: PPP1CB were changed from Rasopathy with developmental delay, short stature and sparse slow-growing hair to Noonan syndrome-like disorder with loose anlagen hair 2, OMIM # 617506 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4513 | PRKD1 |
Zornitza Stark edited their review of gene: PRKD1: Added comment: PMID: 27479907 (2016): three individuals reported, two with the c.1774G>A variant and one with the c.896T>G variant. All had congenital heart disease, two had some developmental delay, and two had variable features of ectodermal dysplasia, including sparse hair, dry skin, thin skin, fragile nails, premature loss of primary teeth, and small widely spaced teeth; the third individuals had a 'disorganized eyebrow.' PMID: 32817298 (2020) - Two additional unrelated cases with de novo variants, c.1774G>C and c.1808G>A, and telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease. Functional analysis using in vitro kinase assays with recombinant proteins showed that the c.1808G>A, p.(Arg603His) variant represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The c.1774G>C, p.(Gly592Arg) variant in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation. c.1774G>C, p.(Gly592Arg) is recurrent, reported in 3/5 individuals.; Changed publications: 27479907, 32817298; Changed phenotypes: Congenital heart defects and ectodermal dysplasia, MIM#617364; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Fetal anomalies v0.4196 | ALG14 | Zornitza Stark Phenotypes for gene: ALG14 were changed from Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036; Disorder of N-glycosylation to Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4165 | RNF113A |
Chirag Patel gene: RNF113A was added gene: RNF113A was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: RNF113A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: RNF113A were set to PMID: 25612912; 31793730; 31880405 Phenotypes for gene: RNF113A were set to Trichothiodystrophy 5, nonphotosensitive; OMIM #300953 Review for gene: RNF113A was set to GREEN Added comment: Four families reported, two with same variant. Clinical features include ID, microcephaly, IUGR/growth failure, hypogonadism, and sparse/brittle hair. One of the families had antenatal presentation. Sources: Expert list |
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| Fetal anomalies v0.4132 | ALG14 |
Belinda Chong gene: ALG14 was added gene: ALG14 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ALG14 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ALG14 were set to 23404334; 28733338; 30221345; 23404334; 28733338 Phenotypes for gene: ALG14 were set to Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036; Disorder of N-glycosylation Review for gene: ALG14 was set to GREEN gene: ALG14 was marked as current diagnostic Added comment: Three OMIM disorders however, only Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036 with prenatal manifestations. 5 individuals from unrelated families described in the literature: one with myasthenic syndrome, no report of ID; second with predominantly ID phenotype; and three more with a neurodegenerative phenotype. ALG14 is part of the UDP-GlcNAc transferase, which catalyzes a key step in endoplasmic reticulum N-linked glycosylation. The three OMIM disorders may represent a spectrum of severity for CDG. Sources: Literature |
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| Fetal anomalies v0.3567 | RIN2 | Zornitza Stark Phenotypes for gene: RIN2 were changed from MACROCEPHALY, ALOPECIA, CUTIS LAXA, AND SCOLIOSIS TALL FOREHEAD, SPARSE HAIR, SKIN HYPEREXTENSIBILITY, AND SCOLIOSIS to Macrocephaly, alopecia, cutis laxa, and scoliosis, MIM#613075 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3544 | RAB11A |
Zornitza Stark changed review comment from: Five individuals reported with DNMs and neurodevelopmental phenotypes as part of this paper; however, clinical details are sparse. Emerging gene, phenotype not yet clearly delineated. Sources: Literature; to: Five individuals reported with DNMs and neurodevelopmental phenotypes as part of this paper; however, clinical details are sparse. Emerging gene, phenotype not yet clearly delineated. Clinical presentation is post-natal. Sources: Literature |
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| Fetal anomalies v0.3151 | PPP1R13L |
Krithika Murali gene: PPP1R13L was added gene: PPP1R13L was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PPP1R13L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPP1R13L were set to 32666529; 28864777 Phenotypes for gene: PPP1R13L were set to Dilated cardiomyopathy, onset in infancy; Cleft lip and palate Review for gene: PPP1R13L was set to GREEN Added comment: No new information since last PanelApp review June 2021 -- At least 6 unrelated families. NMD-predicted, missense and stop-loss (extension) variants have been reported in individuals with autosomal recessive PPP1R13L-related syndrome. Patients described with biallelic pathogenic variants in PPP1R13L all had severe infantile-onset dilated cardiomyopathy, with additional features including cleft lip and palate, wedge-shaped teeth, and sparse, dry, woolly hair described in several individuals. Death due to HF progression before 5yo reported in cases that didn't receive a heart transplant. Cognitive delay also reported in two unrelated individuals (PMID: 28069640, PMID: 32666529). Sources: Literature |
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| Fetal anomalies v0.3151 | LRP6 |
Krithika Murali gene: LRP6 was added gene: LRP6 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: LRP6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: LRP6 were set to 16126904; 30950205; 26387593; 26963285; 28813618; 29500247; 33164649; 34306029 Phenotypes for gene: LRP6 were set to Tooth agenesis, selective, 7 - MIM#616724; cleft lip/palate Review for gene: LRP6 was set to AMBER Added comment: LoF variants known to be associated with tooth agenesis. In addition, x2 unrelated families from 2 different studies with heterozygous LRP6 variant had tooth agenesis and cleft lip/palate (PMID 29500247; 26963285). Growth failure reported in some individuals but unclear if prenatal in onset (PMID 26963285). Minor finger/ear anomalies reported in x2 patients (PMID 26387593; 30950205)- unlikely to be detected antenatally and one of the reported patients (30950205) had x2 chromosome deletions, one of which involved LRP6 and multiple other genes. --- PMID: 34306029 Huang et al 2021 - Heterozygous LRP6: c.2570G > A (p.R857H), harbored by six members of a Chinese family, including 4 with tooth agenesis. Sparse hair another phenotypic feature. PMID: 33164649 Yu et al 2021 - identified 4 novel LRP6 heterozygous mutations in 4 of 77 oligodontia patients. One patient with a nonsense paternally inherited variant had a hypohidrotic ectodermal dysplasia phenotype - no antenatal features, father had oligodontia. Supportive functional evidence PMID: 29500247 Basha et al 2018 - Nonsense LRP6 variant identified in a family with cleft lip/palate. Proband had bilateral cleft lip and palate with missing upper lateral incisors, mother had bilateral cleft lip. x1 unaffected brother but family members not reassessed for oligodontia after variant identified. PMID: 28813618 Dinckan et al 2018 - heterozygous splice site LRP6 variant identified in 1 family with isolated tooth agenesis. Affected family members also had mild periocular hyperpigmentation and hypoplastic alae nasi - thought to be unrelated to phenotype PMID: 26963285 Ockeloen et al 2016 - frameshift variant identified in patient with tooth agenesis and orofacial clefting - boy born with bilateral cleft lip, L) sided cleft of the alveolus and complete cleft of the hard and soft palate. Also noted to have growth retardation, hypermetropia and small median alveolar manibular cleft. Maternal relatives with variant had severe tooth agenesis but no clefting. Canonical splice site variant identified in a patient with isolated severe tooth agenesis. Targeted resequencing showed statistically significant enrichment of unique LRP6 variants in tooth agenesis patients (7/67 versus 13/706 controls), not orofacial clefting cohort. 4/7 of these patients required growth hormone therapy and 3/7 had clinodactyly in addition to dental anomalies. PMID: 26387593 – Massink et al 2015 - x4 LoF heterozygous LRP6 variants identified in 4 unrelated families with isolated severe tooth agenesis. All affected members of one family showed minor anatomical variation of the ear and underdevelopment of the thumb PMID: 30950205 Ross et al 2019 - Proband with oligodontia and thrombocytopenia, also had mild finger and ear anomalies. Array revealed an interstitial loss of 150 kb in 8p23.1 encompassing MCPH1 and ANGPT2 and an interstitial loss of 290 kb in 12p13.2 encompassing ETV6, BCL2L14 and LRP6. Sources: Literature |
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| Fetal anomalies v0.2249 | HRAS | Zornitza Stark changed review comment from: Well established gene-disease association, over 100 affected individuals reported with a characteristic coarse facies, short stature, distinctive hand posture and appearance, severe feeding difficulty, and failure to thrive. Other features include cardiac anomalies and developmental disability. Facial warts, particularly nasolabial, are often present in childhood.; to: Well established gene-disease association, over 100 affected individuals reported with a characteristic coarse facies, short stature, distinctive hand posture and appearance, severe feeding difficulty, and failure to thrive. Other features include cardiac anomalies and developmental disability. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1765 | GZF1 | Ain Roesley reviewed gene: GZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33009817, 28475863; Phenotypes: Joint laxity, short stature, and myopia, MIM# 617662, Larsen-like syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1605 | FLNB | Zornitza Stark Phenotypes for gene: FLNB were changed from BOOMERANG DYSPLASIA; SPONDYLOCARPOTARSAL SYNOSTOSIS SYNDROME; ATELOSTEOGENESIS TYPE 3; AUTOSOMAL DOMINANT LARSEN SYNDROME; ATELOSTEOGENESIS TYPE 1 to Larsen syndrome, MIM#150250; Atelosteogenesis, type I, MIM# 108720; Atelosteogenesis, type III, MIM# 108721; Boomerang dysplasia, MIM# 112310; Spondylocarpotarsal synostosis syndrome, MIM# 272460 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1604 | FLNB | Zornitza Stark edited their review of gene: FLNB: Changed rating: GREEN; Changed phenotypes: Larsen syndrome, MIM#150250, Atelosteogenesis, type I, MIM# 108720, Atelosteogenesis, type III, MIM# 108721, Boomerang dysplasia, MIM# 112310, Spondylocarpotarsal synostosis syndrome, MIM# 272460; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1469 | ZNF699 |
Krithika Murali gene: ZNF699 was added gene: ZNF699 was added to Fetal anomalies. Sources: Literature,Expert list Mode of inheritance for gene: ZNF699 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZNF699 were set to 33875846 Phenotypes for gene: ZNF699 were set to DEGCAGS syndrome - #619488 Review for gene: ZNF699 was set to GREEN Added comment: DEGCAGS syndrome is an autosomal recessive syndromic neurodevelopmental disorder characterized by global developmental delay, coarse and dysmorphic facial features, and poor growth and feeding from infancy. Affected individuals have variable systemic manifestations often with significant structural defects of the cardiovascular, genitourinary, gastrointestinal, and/or skeletal systems. Additional features may include sensorineural hearing loss, hypotonia, anemia or pancytopenia, and immunodeficiency with recurrent infections. Sources: Literature, Expert list |
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| Fetal anomalies v0.275 | B3GAT3 | Zornitza Stark changed review comment from: Established gene-disease association.; to: Established gene-disease association. 26 patients from 13 families with variable phenotypes resembling Larsen, Antley-Bixler, Shprintzen-Goldberg, and Geroderma osteodysplastica syndromes. Multiple skeletal and cardiac abnormalities reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.183 | ARSE | Zornitza Stark Marked gene: ARSE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.183 | ARSE | Zornitza Stark Gene: arse has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.183 | ARSE | Zornitza Stark Phenotypes for gene: ARSE were changed from CHONDRODYSPLASIA PUNCTATA 1, X-LINKED to Chondrodysplasia punctata, X-linked recessive, MIM# 302950 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.182 | ARSE | Zornitza Stark changed review comment from: Well established gene-disease association. Note HGNC approved name is ARSL.; to: Well established gene-disease association. Note HGNC approved name is ARSL. Multiple skeletal anomalies detectable prenatally. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | RIN2 |
Zornitza Stark gene: RIN2 was added gene: RIN2 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: RIN2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: RIN2 were set to MACROCEPHALY, ALOPECIA, CUTIS LAXA, AND SCOLIOSIS TALL FOREHEAD, SPARSE HAIR, SKIN HYPEREXTENSIBILITY, AND SCOLIOSIS |
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| Fetal anomalies v0.0 | DPH1 |
Zornitza Stark gene: DPH1 was added gene: DPH1 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: DPH1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DPH1 were set to 25558065; 32732226; 30877278; 29362492 Phenotypes for gene: DPH1 were set to Developmental delay with short stature, dysmorphic facial features, and sparse hair, OMIM:616901 |
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| Fetal anomalies v0.0 | PPP1CB |
Zornitza Stark gene: PPP1CB was added gene: PPP1CB was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: PPP1CB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: PPP1CB were set to Rasopathy with developmental delay, short stature and sparse slow-growing hair |
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| Fetal anomalies v0.0 | FLNB |
Zornitza Stark gene: FLNB was added gene: FLNB was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: FLNB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: FLNB were set to BOOMERANG DYSPLASIA; SPONDYLOCARPOTARSAL SYNOSTOSIS SYNDROME; ATELOSTEOGENESIS TYPE 3; AUTOSOMAL DOMINANT LARSEN SYNDROME; ATELOSTEOGENESIS TYPE 1 |
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| Fetal anomalies v0.0 | ARSE |
Zornitza Stark gene: ARSE was added gene: ARSE was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ARSE was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ARSE were set to CHONDRODYSPLASIA PUNCTATA 1, X-LINKED |
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