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| Intellectual disability syndromic and non-syndromic v1.49 | TRPM7 | Zornitza Stark Phenotypes for gene: TRPM7 were changed from Familial primary hypomagnesemia, MONDO:0018100, TRPM7-related to Familial primary hypomagnesaemia, MONDO:0018100, TRPM7-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v1.47 | TRPM7 |
Zornitza Stark gene: TRPM7 was added gene: TRPM7 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: TRPM7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRPM7 were set to 35561741; 35712613; 39099563 Phenotypes for gene: TRPM7 were set to Familial primary hypomagnesemia, MONDO:0018100, TRPM7-related Review for gene: TRPM7 was set to GREEN Added comment: Protein expressed in the distal tubule, related to TRPM6. Postulated link with hypoMg with secondary hypoCa. PMID 35561741: two families reported with dominant inheritance. F1: three affected individuals with splicing variant; some supportive functional data. F2: single affected individual, de novo missense variant. PMID 35712613: de novo missense variant in an individual with hypoMg. PMID 39099563: three affected individuals with missense variants, all de novo. Probands had DD, two had seizures. Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v0.5867 | MAGT1 | Zornitza Stark Phenotypes for gene: MAGT1 were changed from Congenital disorder of glycosylation, type Icc, OMIM #301031; Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia, OMIM #300853 to X-linked intellectual disability MONDO:0100284; Congenital disorder of glycosylation, type Icc, OMIM #301031 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.4987 | HECW2 |
Zornitza Stark changed review comment from: Two probands reported with biallelic variants and putative loss of function mechanism of disease (compared to the established gain of function monoallelic disease) PMID: 35753050 - Caucasian girl who presented a severe neurodevelopmental disorder with drug-resistant epilepsy, hypotonia, severe gastro-esophageal reflux and brain magnetic resonance imaging anomalies with a homozygous splice variant that causes in-frame elimination of exon 22 (c.3917+2_3917+12delinsG r.3766_3917+1del p.Leu1256_Trp1306del). Protein expression level was reduced by 60%, suggesting a partial loss-of-function mechanism of disease. PMID: 35487419 - homozygous nonsense variant (c.736C>T; p.Arg246*) identified in a proband from a Moroccan consanguineous family, with developmental delay, intellectual disability, hypotonia, generalized tonico-clonic seizures and a persistent tilted head.; to: Two probands reported with biallelic variants and putative loss of function mechanism of disease (compared to the established gain of function monoallelic disease) PMID: 35753050 - Caucasian girl who presented a severe neurodevelopmental disorder with drug-resistant epilepsy, hypotonia, severe gastro-esophageal reflux and brain magnetic resonance imaging anomalies with a homozygous splice variant that causes in-frame elimination of exon 22 (c.3917+2_3917+12delinsG r.3766_3917+1del p.Leu1256_Trp1306del). Protein expression level was reduced by 60%, suggesting a partial loss-of-function mechanism of disease. PMID: 35487419 - homozygous nonsense variant (c.736C>T; p.Arg246*) identified in a proband from a Moroccan consanguineous family, with developmental delay, intellectual disability, hypotonia, generalized tonico-clonic seizures and a persistent tilted head. Association with bi-allelic variants is AMBER. |
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| Intellectual disability syndromic and non-syndromic v0.4987 | HECW2 |
Zornitza Stark edited their review of gene: HECW2: Added comment: Two probands reported with biallelic variants and putative loss of function mechanism of disease (compared to the established gain of function monoallelic disease) PMID: 35753050 - Caucasian girl who presented a severe neurodevelopmental disorder with drug-resistant epilepsy, hypotonia, severe gastro-esophageal reflux and brain magnetic resonance imaging anomalies with a homozygous splice variant that causes in-frame elimination of exon 22 (c.3917+2_3917+12delinsG r.3766_3917+1del p.Leu1256_Trp1306del). Protein expression level was reduced by 60%, suggesting a partial loss-of-function mechanism of disease. PMID: 35487419 - homozygous nonsense variant (c.736C>T; p.Arg246*) identified in a proband from a Moroccan consanguineous family, with developmental delay, intellectual disability, hypotonia, generalized tonico-clonic seizures and a persistent tilted head.; Changed publications: 29807643, 29395664, 27334371, 27389779, 35753050, 35487419; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Intellectual disability syndromic and non-syndromic v0.4703 | CNNM2 | Ain Roesley Phenotypes for gene: CNNM2 were changed from to Hypomagnesemia 6, renal MIM#613882; Hypomagnesemia, seizures, and mental retardation MIM#616418 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.4702 | CNNM2 | Ain Roesley reviewed gene: CNNM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34604137, 35170241; Phenotypes: Hypomagnesemia 6, renal MIM#613882, Hypomagnesemia, seizures, and mental retardation MIM#616418; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.4486 | RBL2 | Alison Yeung Phenotypes for gene: RBL2 were changed from Intellectual disability; Brunet-Wagner neurodevelopmental syndrome MIM#619690 to Intellectual disability; Brunet-Wagner neurodevelopmental syndrome MIM#619690 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.4486 | RBL2 | Alison Yeung Phenotypes for gene: RBL2 were changed from Intellectual disability to Intellectual disability; Brunet-Wagner neurodevelopmental syndrome MIM#619690 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.4482 | RBL2 | Elena Savva reviewed gene: RBL2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33980986, 32105419, 9806916; Phenotypes: Severe motor and cognitive impairment, Intellectual disability, Brunet-Wagner neurodevelopmental syndrome MIM#619690; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.3452 | MSL3 | Zornitza Stark commented on gene: MSL3: Well established ID gene. 2021 paper documents findings in 25 individuals. Variants found to be clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.3384 | SCAMP5 | Zornitza Stark edited their review of gene: SCAMP5: Added comment: PMID 33390987: Four unrelated individuals reported with same de novo missense variant, p. Gly180Trp. The onset age of seizures was ranged from 6 to 15 months. Patients had different types of seizures, including focal seizures, generalized tonic-clonic seizures and tonic seizure. One patient showed typical autism spectrum disorder (ASD) symptoms. Electroencephalogram (EEG) findings presented as focal or multifocal discharges, sometimes spreading to generalization. Brain magnetic resonance imaging (MRI) abnormalities were present in each patient. Severe intellectual disability and language and motor developmental disorders were found in our patients, with all patients having poor language development and were nonverbal at last follow-up. All but one of the patients could walk independently in childhood, but the ability to walk independently in one patient had deteriorated with age. All patients had abnormal neurological exam findings, mostly signs of extrapyramidal system involvement. Dysmorphic features were found in 2/4 patients, mainly in the face and trunk.; Changed rating: GREEN; Changed publications: 33390987; Changed phenotypes: Intellectual disability, seizures, autism; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.3098 | SETD1A |
Zornitza Stark changed review comment from: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism. In addition, there are 3 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.; to: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism. In addition, there are 4 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders. |
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| Intellectual disability syndromic and non-syndromic v0.3097 | SETD1A |
Zornitza Stark edited their review of gene: SETD1A: Added comment: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism. In addition, there are 3 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.; Changed phenotypes: Epilepsy, early-onset, with or without developmental delay, MIM# 618832, Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056 |
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| Intellectual disability syndromic and non-syndromic v0.2830 | SOX6 | Zornitza Stark Phenotypes for gene: SOX6 were changed from ADHD; Craniosynostosis; Osteochondromas to ADHD; Craniosynostosis; Osteochondromas; Tolchin-Le Caignec syndrome, MIM#618971 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.2829 | SOX6 | Zornitza Stark edited their review of gene: SOX6: Changed rating: GREEN; Changed phenotypes: Tolchin-Le Caignec syndrome, MIM#618971; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.1428 | ATP1A1 |
Zornitza Stark gene: ATP1A1 was added gene: ATP1A1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature Mode of inheritance for gene: ATP1A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP1A1 were set to 30388404 Phenotypes for gene: ATP1A1 were set to Intellectual disability; seizures; hypomagnesaemia Review for gene: ATP1A1 was set to GREEN Added comment: Three infants with de novo missense variants in this gene; seizures persisted despite correction of magnesium, intellectual disability is part of the phenotype. Note gene is also linked to CMT and possibly HSP. Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v0.405 | MAGT1 |
Chirag Patel Source Genetic Health Queensland was removed from MAGT1. Source Expert list was added to MAGT1. Mode of inheritance for gene MAGT1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: MAGT1 were changed from to Congenital disorder of glycosylation, type Icc, OMIM #301031; Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia, OMIM #300853 Publications for gene MAGT1 were changed from PMID: 31036665 to PMID: 31036665 |
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| Intellectual disability syndromic and non-syndromic v0.404 | MAGT1 | Chirag Patel reviewed gene: MAGT1: Rating: AMBER; Mode of pathogenicity: None; Publications: PubMed: 31036665; Phenotypes: Congenital disorder of glycosylation, type Icc, OMIM #301031, Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia, OMIM #300853; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.317 | GNE | Zornitza Stark Marked gene: GNE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.317 | GNE | Zornitza Stark Gene: gne has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.317 | GNE | Zornitza Stark Phenotypes for gene: GNE were changed from to Sialuria, MIM#269921 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.316 | GNE | Zornitza Stark Mode of inheritance for gene: GNE was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.315 | GNE | Zornitza Stark reviewed gene: GNE: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sialuria, MIM#269921; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.0 | GNE |
Zornitza Stark gene: GNE was added gene: GNE was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland Mode of inheritance for gene: GNE was set to Unknown |
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