Brain channelopathy
Gene: CACNA1A
Four infants, all presenting with hypotonia, mild facial dysmorphic features, encephalopathy, and seizures, born
to consanguineous parents. Testing was only performed on two of the newborns in the family. A novel homozygous nonsense c.2767C>T p.(Arg932*) variant in the exon 19 of the CACNA1A gene (NM_001127221.1). Segregation analysis showed that both parents were heterozygous carriers and they were diagnosed with EA2.
Well established association between mono-allelic variants and a number of phenotypes including episodic ataxia.Created: 4 Dec 2021, 8:20 a.m. | Last Modified: 4 Dec 2021, 8:20 a.m.
Panel Version: 1.70
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hypotonia; encephalopathy
Publications
Comment when marking as ready: Added 'treatable' tagsCreated: 18 Jan 2017, 1:04 p.m.
A range of phenotypes are associated with mutations in CACNA1A. as a general rule, all FHM1 mutations are missense
mutations and most, but not all, EA2 mutations disrupt the open reading frame, likely subject to nonsense mediated
mRNA decay or rapid degradation of truncated protein products. Spinocerebellar ataxia type 6 (SCA6) are caused by CAG repeat expansion the in carboxy terminus.Created: 6 Jan 2017, 9:43 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
episodic ataxia type 2 (EA2), familial hemiplegic migraine type 1 (FHM1), spinocerebellar ataxia type 6 (SCA6)
Publications
Comment on list classification: Promoted from red to green as this gene is on the Brain Channel NGS Panel in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual.Created: 10 Jun 2016, 3:18 p.m.
Phenotypes for gene: CACNA1A were changed from episodic ataxia type 2 (EA2),108500; familial hemiplegic migraine type 1, 141500 to Episodic ataxia, type 2, OMIM:108500; Migraine, familial hemiplegic, 1, OMIM:141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500
Publications for gene: CACNA1A were set to 17575281; 21734179
Phenotypes for CACNA1A were set to episodic ataxia type 2 (EA2),108500; familial hemiplegic migraine type 1, 141500;
This gene has been classified as Green List (High Evidence).
Promoted to V1. January 23 2017
This gene has been classified as Green List (High Evidence).
Phenotypes for CACNA1A were set to episodic ataxia type 2 (EA2), familial hemiplegic migraine type 1; dominant, long duration episodic ataxia
Publications for CACNA1A were set to 17575281
Mode of inheritance for CACNA1A was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for CACNA1A were set to EPISODIC ATAXIA, TYPE 2; MIGRAINE, FAMILIAL HEMIPLEGIC, 1; dominant, long duration episodic ataxia
This gene has been classified as Green List (High Evidence).
CACNA1A was added to Brain channelopathypanel. Sources: UKGTN
CACNA1A was added to Brain channelopathypanel. Sources: Eligibility statement prior genetic testing