title: Missense CACNA1A mutation causing episodic ataxia type 2.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  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.
  
  
  METHODS
  All 47 exons of CACNA1A were screened by a combination of single-strand conformer polymorphism and sequencing analysis.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: INSERM EPI 99-21, Faculté de Médecine Lariboisière, 10, Avenue de Verdun, 75010 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Denier
authors.forename: A
authors.initials: A
authors.lastname: Ducros
authors.forename: A
authors.initials: A
authors.lastname: Durr
authors.forename: B
authors.initials: B
authors.lastname: Eymard
authors.forename: B
authors.initials: B
authors.lastname: Chassande
authors.forename: E
authors.initials: E
authors.lastname: Tournier-Lasserve
mesh_terms: D015220:Calcium Channels / Q000235:genetics*; D002524:Cerebellar Ataxia / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type