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| Intellectual disability syndromic and non-syndromic v1.177 | SREK1 |
Sangavi Sivagnanasundram gene: SREK1 was added gene: SREK1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: SREK1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SREK1 were set to 40549565 Phenotypes for gene: SREK1 were set to Prader-Willi-like syndrome, SREK1-related MONDO:0008300 Review for gene: SREK1 was set to AMBER Added comment: Three Pakistani probands from three consanguineous families identified with biallelic variants in SREK1. Affected individuals presented with hyperphagic obesity and neurodevelopmental delay. They also presented with psychological and behavioural issues and were phenotypically similar to Prader-Willi affected individuals. ID/DD is a feature in the affected individuals. Further testing was conducted using human induced pluripotent stem cell (iPSC) -derived neurons followed by RNA sequencing conducted on the neurons. The results of the assay was suggestive that variants located in the RNA recognition domain (residues 19–96 and 173–256) of SREK1 downregulation of SNORD115 and SNORD116 leading to Prader-Willi-like phenotype however proper validation and controls weren't used. No relevant mouse models were identified on IMPC (international mouse phenotype consortium) to further support gene-disease association there gene reviewed as Amber. Variants identified in SREK1 - AF's from gnomADv4.1 P95L - absent in gnomAD v4.1 T194M - EAS PopMax AF - 0.03787% (47 hets) E601K - SAS PopMax AF - 0.01319% (12 hets) Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v1.120 | EIF3K |
Sangavi Sivagnanasundram gene: EIF3K was added gene: EIF3K was added to Intellectual disability syndromic and non-syndromic. Sources: Other Mode of inheritance for gene: EIF3K was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EIF3K were set to 40219605 Phenotypes for gene: EIF3K were set to EIF3K-related neurodevelopmental disorder, MONDO:0700092 Review for gene: EIF3K was set to RED Added comment: More evidence is required determine whether variants in EIF3K result in a neurodevelopmental disorder. Only two variants have been reported. Four individuals with global DD, microcephaly, and short stature. Three out of the four individuals had the recurrent homozygous EIF3K (Asp43Gly - gnomAD v4.1 GrpMax FAF - 0.06044%) variant whilst another individual has homozygous intronic EIF3K variant, c.355-13A>G (gnomADv4.1 GrpMax FAF = 0.002551%). The 3 individuals of Puerto Rican ancestry with the recurrent missense variant also had homozygous SYNE4 variant (Arg119Trp) identified which the author related to the probands' hearing loss phenotype. The Asp43Gly missense variant could potentially be a founder variant however only three families with affected probands have been reported with the variant. Sources: Other |
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| Intellectual disability syndromic and non-syndromic v0.5697 | MAX | Zornitza Stark Phenotypes for gene: MAX were changed from Syndromic disease (MONDO:0002254), MAX-related to Polydactyly-macrocephaly syndrome, MIM# 620712 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5665 | MAX | Zornitza Stark Marked gene: MAX as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5665 | MAX | Zornitza Stark Gene: max has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5665 | MAX | Zornitza Stark Classified gene: MAX as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5665 | MAX | Zornitza Stark Gene: max has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5661 | MAX |
Rylee Peters gene: MAX was added gene: MAX was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAX were set to 38141607 Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related Review for gene: MAX was set to GREEN Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain. Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae. Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc. Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v0.2235 | SOBP | Zornitza Stark Phenotypes for gene: SOBP were changed from Mental retardation, anterior maxillary protrusion, and strabismus, MIM# 613671 to Mental retardation, anterior maxillary protrusion, and strabismus, MIM# 613671 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.2234 | SOBP | Zornitza Stark Phenotypes for gene: SOBP were changed from to Mental retardation, anterior maxillary protrusion, and strabismus, MIM# 613671 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.2231 | SOBP | Zornitza Stark reviewed gene: SOBP: Rating: RED; Mode of pathogenicity: None; Publications: 21035105; Phenotypes: Mental retardation, anterior maxillary protrusion, and strabismus, MIM# 613671; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.1355 | GABRA5 |
Chirag Patel gene: GABRA5 was added gene: GABRA5 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature Mode of inheritance for gene: GABRA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GABRA5 were set to PMID: 31056671; 29961870 Phenotypes for gene: GABRA5 were set to Epileptic encephalopathy, early infantile, 79; OMIM #618559 Review for gene: GABRA5 was set to GREEN Added comment: 3 unrelated patients with de novo heterozygous missense mutations in GABRA5 gene. In vitro functional expression studies in HEK293 cells showed that the mutant subunit was expressed at the surface and incorporated into the channel, but the mutant channel was 10 times more sensitive to GABA compared to wildtype. This increased sensitization resulted in increased receptor desensitization to GABA, with a reduced maximal GABA-evoked current and impaired capacity to pass GABAergic chloride current. Sources: Literature |
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