Early onset or syndromic epilepsy
Gene: BET1
Comment on classification of this gene: The rating for this gene should be RED. This gene has been implicated in epilepsy, as identified from biallelic variants from only one individual, and supported by results from functional studies.
Three individuals from two unrelated families were identified with biallelic variants in BET1. Out of these, family 1 with only one patient harboured compound heterozygous variants (c.202G>C/ p.Asp68His & c.134delC/ p.Ala45ValfsTer2) and family 2 with two patients harboured homozygous variant (c.152T>G/ p.Ile51Ser). Although, all three patients were reported with severe congenital muscular dystrophy, only the individual with compound heterozygous variants was reported with epilepsy from this study.
Functional studies showed that the missense variant (p.Asp68His) acts as a complex splice variant and causes a reduction of BET1 protein in patient cells with impaired vesicular traffic. Analysis of cells from the second patient with the p.Ile51Ser missense variant identified normal levels of BET1 protein. ERGIC‐53 was identified as a novel interaction partner of BET1 and p.Ile51Ser BET1 missense protein resulted in impaired interaction with ERGIC‐53.
BET1 has not yet been associated with either congenital muscular dystrophy or epilepsy in OMIM or in Gene2Phenotype.Created: 12 Dec 2022, 5:15 p.m. | Last Modified: 12 Dec 2022, 5:15 p.m.
Panel Version: 3.1
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Epilepsy, MONDO:0005027
Publications
3 reported individuals from two families with biallelic variants and functional data supporting the role of the variants in the phenotype. Enough evidence for green rating.
Sources: LiteratureCreated: 7 Dec 2021, 1:46 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Epilepsy; congenical musculara dystrophy
Publications
Phenotypes for gene: BET1 were changed from Epilepsy; congenical musculara dystrophy to Epilepsy, MONDO:0005027
Publications for gene: BET1 were set to PMID: 34779586
Gene: bet1 has been classified as Red List (Low Evidence).
gene: BET1 was added gene: BET1 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: BET1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BET1 were set to PMID: 34779586 Phenotypes for gene: BET1 were set to Epilepsy; congenical musculara dystrophy Penetrance for gene: BET1 were set to Complete Review for gene: BET1 was set to GREEN