Congenital myopathy

Gene: CASQ1

Amber List (moderate evidence)

CASQ1 (calsequestrin 1)
EnsemblGeneIds (GRCh38): ENSG00000143318
EnsemblGeneIds (GRCh37): ENSG00000143318
OMIM: 114250, Gene2Phenotype
CASQ1 is in 4 panels

5 reviews

Zornitza Stark (Australian Genomics)

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

Louise Daugherty (Genomics England Curator)

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.

Rachael Mein (Viapath at Guy's Hospital)

I don't know

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

Phenotypes
Myopathy, vacuolar, with CASQ1 aggregates 616231

Publications

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

Helen Brittain (Genomics England Curator)

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.

Anna Sarkozy (Great Ormond Street Hospital)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal

Phenotypes
Vacuolar myopathy with CASQ1 aggregates (VMCQA)

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • London South GLH
  • Expert Review Amber
Phenotypes
  • Vacuolar myopathy with CASQ1 aggregates (VMCQA)
  • Myopathy, vacuolar, with CASQ1 aggregates, 616231
OMIM
114250
Clinvar variants
Variants in CASQ1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

3 May 2019, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: CASQ1 were changed from Vacuolar myopathy with CASQ1 aggregates (VMCQA) to Vacuolar myopathy with CASQ1 aggregates (VMCQA); Myopathy, vacuolar, with CASQ1 aggregates, 616231

30 Apr 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to CASQ1.

30 Apr 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source London South GLH was added to CASQ1.

7 Mar 2017, Gel status: 2

Gene classified by Genomics England curator

Helen Brittain (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

7 Mar 2017, Gel status: 2

Gene classified by Genomics England curator

Helen Brittain (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

6 Mar 2017, Gel status: 0

Added New Source

Anna Sarkozy (Great Ormond Street Hospital)

CASQ1 was added to Congenital myopathypanel. Sources: UCL

6 Mar 2017, Gel status: 0

Created

Anna Sarkozy (Great Ormond Street Hospital)

CASQ1 was created by anna.sarkozy