Referenced in: none

Automatically associated channels: Cav2.1 , Kv2.1

Title: Missense CACNA1A mutation causing episodic ataxia type 2.

Authors: C Denier, A Ducros, A Durr, B Eymard, B Chassande, E Tournier-Lasserve

Journal, date & volume: Arch. Neurol., 2001 Feb , 58, 292-5

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11176968

Abstract
To characterize the nature of CACNA1A mutation in a previously unreported family with episodic ataxia type 2 (EA2) and to better delineate EA2 clinical features.Episodic ataxia type 2 is an autosomal dominant disorder characterized by the recurrence of acetazolamide-responsive spells of cerebellar ataxia, usually starting during childhood or adolescence. The mutated gene, CACNA1A, is located on chromosome 19 and encodes the alpha1A subunit voltage-dependent calcium channel. So far, most CACNA1A mutations detected in patients with EA2 have led to a truncated CACNA1A protein, whereas missense mutations cause familial hemiplegic migraine.All 47 exons of CACNA1A were screened by a combination of single-strand conformer polymorphism and sequencing analysis.A CACNA1A missense mutation, Glu 1757 Lys, was identified. It was absent in 200 control chromosomes. It is predicted to result in an amino acid substitution at a highly phylogenetically conserved position, within a domain that plays a major role in the function of the channel.The Glu 1757 Lys missense mutation is likely to be pathogenic, causing episodic ataxia within a family whose phenotype is indistinguishable from EA2 except for a slightly later age of onset. These data strongly suggest that additional work is needed to fully establish genotype/phenotype correlations for CACNA1A mutations.