Congenital muscular dystrophy

Gene: BET1

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 1:47 p.m. | Last Modified: 26 Sep 2024, 1:47 p.m.

Panel Version: 4.28

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

this gene should be included as green gene given recent publications on biallelic variants in patients from 2 unrelated families presenting with severe congenital muscular dystrophy and epilepsy. the BET1 gene variants result in low BET1 protein levels and impaired ER‐to‐Golgi transport.

Created: 24 Mar 2023, 1:28 p.m. | Last Modified: 24 Mar 2023, 1:28 p.m.

Panel Version: 4.1

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
congenital muscular dystrophy with epilepsy

Publications

• PMID: 34779586

Mode of pathogenicity
Other

Green List (high evidence)

Comment on classification of this gene: As reviewed by Dmitrijs Rots, the rating for this gene should be GREEN. This gene has been implicated in congenital muscular dystrophy, as identified from biallelic variants from two unrelated cases 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). All three patients were reported with severe congenital muscular dystrophy and individual with compound heterozygous variants was reported with epilepsy.

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 congenital muscular dystrophy in OMIM or in Gene2Phenotype and the publication describing this association was from the last year.

Created: 12 Dec 2022, 5:06 p.m. | Last Modified: 12 Dec 2022, 5:06 p.m.

Panel Version: 3.1

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital muscular dystrophy, MONDO:0019950

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.

Created: 7 Dec 2021, 1:43 p.m. | Last Modified: 7 Dec 2021, 1:43 p.m.

Panel Version: 2.21

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital muscular dystrophy; epilepsy

Publications

• PMID: 34779586

I don't know

Initial gene list (Congenital Muscular Dystrophy Gene Panel 207-London South GLH.xlsx) collated by Rachael Mein, Viapath Guy's Hospital February 2019 on behalf of London South GLH for the GMS Neurology specialist test group.

Created: 29 Apr 2019, 3:37 p.m.

I don't know

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital muscular dystrophy with epilepsy