Early onset or syndromic epilepsy

Gene: BET1

Red List (low evidence)

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

• 34779586

Green List (high evidence)

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: Literature

Created: 7 Dec 2021, 1:46 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy; congenical musculara dystrophy

Publications

• PMID: 34779586