Muscular dystrophy and myopathy_Paediatric

Gene: CACNA1S

Green List (high evidence)

CACNA1S (calcium voltage-gated channel subunit alpha1 S)
EnsemblGeneIds (GRCh38): ENSG00000081248
EnsemblGeneIds (GRCh37): ENSG00000081248
OMIM: 114208, Gene2Phenotype
CACNA1S is in 15 panels

3 reviews

Bryony Thompson (Royal Melbourne Hospital)

Green List (high evidence)

At least 5 families with biallelic variants and 3 families with monoallelic missense variants (mainly de novo) with congenital myopathy. A decrease in protein level and a major impairment of Ca2+ release induced by depolarization in cultured myotubes was identified in both the dominant and recessive families. Thus, loss of function is the mechanism of disease for CACNA1S-related congenital myopathy.
Sources: Expert list
Created: 10 May 2023, 2:27 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Congenital myopathy MONDO:0019952

Publications

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

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

11 patients from 7 families reported with perinatal hypotonia and weakness. AR / AD inheritance observed, PMID 28012042
Created: 15 Jun 2020, 8:51 a.m. | Last Modified: 15 Jun 2020, 8:51 a.m.
Panel Version: 0.185

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Myopathy, congenital, due to dihydropyridine receptor defect, MIM# 620246

Publications

Elena Savva (Victorian Clinical Genetics Services)

Green List (high evidence)

PMID: 32104981 - 1 Japanese family with consistent childhood onset hypokalemic periodic paralysis. The proband manifested symptoms at 6 years old and her children at 4- and 2 years of age. Motor and language development normal.

PMID: 19118277 - Arg mutations within the S4 segments are enriched in this gene, including recurring mutations p.Arg528Gly, p.Arg528His, p.Arg1239Gly and p.Arg1239His. One patient with a novel missense was specifically noted as having onset "in the second decade".

PMID: 31380823 - 1 patient with onset at 14 years old following vigorous exercise

PMID: 30325262 - 5 patients with adult onset myopathy (60-80 years old). Some have reported skeletal muscle defects.

PMID: 30319441 - describes both LOF and GOF mechanisms for this gene

Summary: a wide age of onset but multiple paediatric reports.
Sources: Expert list
Created: 15 Jun 2020, 3:47 a.m.

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

Phenotypes
Hypokalemic periodic paralysis, type 1 170400

Publications

Mode of pathogenicity
Other

History Filter Activity

10 May 2023, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: cacna1s has been classified as Green List (High Evidence).

10 May 2023, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: cacna1s has been classified as Green List (High Evidence).

10 May 2023, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Bryony Thompson (Royal Melbourne Hospital)

gene: CACNA1S was added gene: CACNA1S was added to Muscular dystrophy_Paediatric. Sources: Expert list Mode of inheritance for gene: CACNA1S was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: CACNA1S were set to 28012042; 31227654; 33060286 Phenotypes for gene: CACNA1S were set to Congenital myopathy MONDO:0019952 Review for gene: CACNA1S was set to GREEN gene: CACNA1S was marked as current diagnostic