Brain channelopathy

Gene: CACNA1A

Red List (low evidence)

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

• 34267336

Comment when marking as ready: Added 'treatable' tags

Created: 18 Jan 2017, 1:04 p.m.

Green List (high evidence)

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

• 17575281

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.