Referenced in: none

Automatically associated channels: Cav2.1 , Slo1

Title: Late-onset episodic ataxia type 2 associated with a novel loss-of-function mutation in the CACNA1A gene.

Authors: Ester Cuenca-León, Isabel Banchs, Selma A Serra, Pilar Latorre, Noèlia Fernàndez-Castillo, Roser Corominas, Miguel A Valverde, Víctor Volpini, José M Fernández-Fernández, Alfons Macaya, Bru Cormand

Journal, date & volume: J. Neurol. Sci., 2009 May 15 , 280, 10-4

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19232643

Abstract
We report a patient with typical features of episodic ataxia type 2 (EA2) but with onset in the sixth decade and associated interictal hand dystonia. He was found to bear the novel heterozygous missense mutation p.Gly638Asp (c.1913G>A) in the CACNA1A gene. Functional analysis of the mutation on P/Q channels expressed in HEK 293 cells revealed a reduction of Ca(2+) current densities, a left-shift in the apparent reversal potential, the slowing of inactivation kinetics and the increase in the rate of current recovery from inactivation. These results are consistent with a decrease in Ca(2+) permeability through mutant P/Q channels. To our knowledge, this is just the second patient with late onset EA2 linked to a CACNA1A mutation and the first to carry a loss-of-function missense mutation.