Congenital muscular dystrophy and congenital myopathy

Gene: CASQ1

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

Created: 29 Jul 2022, 1:47 p.m. | Last Modified: 29 Jul 2022, 1:47 p.m.

Panel Version: 2.88

Red List (low evidence)

OMIM notes adult onset

PMID: 30258016 - 22 patients (12 families) where 21/22 carried a founder mutation p.Asp244Gly.
- Patients presented with adult onset proximal weakness, quadricep atrophy and 3/22 with cardiac involvement.
- Some patients were asymptomatic and diagnosed by elevated creatine kinase.
- Youngest age at onset was 12 years old, but only 2/22 were symptomatic <30 years of age.

PMID: 25116801 - 8 patients (4 families) with mild myopathy. All patients were heterozygous for the founder mutation p.Asp244Gly. Patients were aged 23-58 years old at the time of analysis, none mentioned to have childhood onset.

PMID: 26136523 - functionally shows that missense cause both wildtype and mutation protein to aggregate and mislocalise -> evidence of dominant negative mechanism. Lack of NMD predicted variants supports this finding.

Summary: Rare reports of childhood onset, none congenital

Created: 15 Jun 2020, 8:40 a.m. | Last Modified: 15 Jun 2020, 8:40 a.m.

Panel Version: 2.5

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Myopathy, vacuolar, with CASQ1 aggregates 616231

Publications

• 30258016
• 25116801
• 26136523

I don't know

Gene rating and review submitted by Rachael Mein, Viapath Guy's Hospital February 2019 on on behalf of London South GLH for the GMS Neurology specialist test group.

Created: 30 Apr 2019, 10:09 a.m.

I don't know

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Myopathy, vacuolar, with CASQ1 aggregates 616231

Publications

• 25116801

Variants in this GENE are reported as part of current diagnostic practice

Comment when marking as ready: Adult affected with mild myopathy and therefore phenotype not appropriate for inclusion on this panel based upon the current evidence.

Created: 7 Mar 2017, 4:27 p.m.

Comment on list classification: Associated with the phenotype but age of onset well into adulthood in most cases found. Therefore not considered appropriate.

Created: 7 Mar 2017, 4:26 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal

Phenotypes
Vacuolar myopathy with CASQ1 aggregates (VMCQA)

Publications

• 25116801