Congenital muscular dystrophy and congenital myopathy

Gene: GOSR2

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 2 May 2024, 3:45 p.m. | Last Modified: 2 May 2024, 3:45 p.m.

Panel Version: 0.229

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Anna Sarkozy (Great Ormond Street Hospital) reviewing this gene on the old GMS Congenital muscular dystrophy panel on 24 Mar 2023 notes (rated Green):'This gene has been implicated in multiple cases of congenital onset muscular dystrophy with raised CK and also evidence of reduced alpha-dystroglycan on muscle pathology.'

Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal

Phenotypes: congenital muscular dystrophy with secondary alpha-dystroglycanopathy

Publications: PMID: 33639315; 33639315

Mode of pathogenicity: Other

Created: 21 Dec 2023, 8:22 p.m. | Last Modified: 21 Dec 2023, 8:22 p.m.

Panel Version: 0.197

Comment on classification of this gene: As reviewed by Zornitza Stark, the rating for this gene should be GREEN. This gene has been implicated in muscular dystrophy, as identified from biallelic variants from five cases from four unrelated families.

All these patients were reported with high creatine kinase (CK) levels and myopathy. Three individuals from two different families displayed congenital hypotonia (PMID:29855340; PMID:33639315), while another individual displayed mild hypotonia (https://doi.org/10.1016/j.nmd.2013.06.404)

Although GOSR2 has already been associated with progressive myoclonic epilepsy 6 (MIM# 614018) in OMIM, it has not yet been associated with congenital muscular dystrophy in OMIM or in Gene2Phenotype. This association has only recently been made in scientific literature.

Created: 12 Dec 2022, 5:28 p.m. | Last Modified: 12 Dec 2022, 5:28 p.m.

Panel Version: 3.5

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy, congenital, with or without seizures, OMIM:620166

Publications

• 29855340
• 33639315
• 34167170

Green List (high evidence)

5 cases from 4 unrelated families with muscular involvement and PME phenotype. All cases had a missense/leaky splice variant with a predicted loss of function variant
PMID: 34167170 - a case with early onset myoclonus epilepsy, ataxia, areflexia, and relatively preserved cognition. Also had high CK and myopathy in a muscle biopsy. Biallelic variants (c.204‐7A>G and c.319C>T, p.Arg107*) and a less severe phenotype.
PMID: 33639315 - a case with congenital hypotonia and persistently elevated creatine kinase levels with biallelic variants (c.430G>T, p.(Gly144Trp) and c.82C>T, p.(Gln28*))
PMID: 29855340 - 2 siblings with hypotonia, muscle weakness, low muscle bulk, and elevated creatine kinase levels with biallelic variants (c.430G>T p.(Gly144Trp) and c.2T>G p.M1?)
DOI:https://doi.org/10.1016/j.nmd.2013.06.404 - an infant with mild hypotonia, severe developmental delay, and increased CK with biallelic variants (c.430G>T p.(Gly144Trp) and c.336+1G>A). Also developed other features of the PME phenotype

Created: 12 Sep 2021, 5:53 a.m. | Last Modified: 12 Sep 2021, 5:53 a.m.

Panel Version: 2.16

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy, progressive myoclonic 6 MIM#614018; congenital muscluar dystrophy

Publications

• 34167170
• 33639315
• 33639315
• 29855340
• DOI:https://doi.org/10.1016/j.nmd.2013.06.404

Red List (low evidence)

GOSR2 is associated with epilepsy in OMIM but no phenotypes in Gene2Phenotype. PMID: 29855340 reported on 2 siblings from a family who have muscular dystrophy who have compound heterozygous variants in the GOSR2 gene. There does not appear to be any relevant animal models. Therefore, this gene should remain red until more evidence is available to support a gene-disease association.

Created: 6 Aug 2019, 2:35 p.m. | Last Modified: 6 Aug 2019, 2:35 p.m.

Panel Version: 1.51

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.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital muscular dystrophy with hypoglycosylation of alpha-dystroglycan

Publications

• 29855340