title: A novel ATP1A2 gene mutation in an Irish familial hemiplegic migraine kindred.
abstract: OBJECTIVE
  We studied a large Irish Caucasian pedigree with familial hemiplegic migraine (FHM) with the aim of finding the causative gene mutation.
  
  
  BACKGROUND
  FHM is a rare autosomal-dominant subtype of migraine with aura, which is linked to 4 loci on chromosomes 19p13, 1q23, 2q24, and 1q31. The mutations responsible for hemiplegic migraine have been described in the CACNA1A gene (chromosome 19p13), ATP1A2 gene (chromosome 1q23), and SCN1A gene (chromosome 2q24).
  
  
  METHODS
  We performed linkage analyses in this family for chromosome 1q23 and performed mutation analysis of the ATP1A2 gene.
  
  
  RESULTS
  Linkage to the FHM2 locus on chromosome 1 was demonstrated. Mutation screening of the ATP1A2 gene revealed a G to C substitution in exon 22 resulting in a novel protein variant, D999H, which co-segregates with FHM within this pedigree and is absent in 50 unaffected individuals. This residue is also highly conserved across species.
  
  
  CONCLUSIONS
  We propose that D999H is a novel FHM ATP1A2 mutation.
authors.affiliation: Department of Neurology, Cork University Hospital, Wilton, Cork, Ireland.
authors.forename: Desiree M
authors.initials: DM
authors.lastname: Fernandez
authors.forename: Collette K
authors.initials: CK
authors.lastname: Hand
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Sweeney
authors.forename: Nollaig A
authors.initials: NA
authors.lastname: Parfrey
mesh_terms: D001224:Aspartic Acid / Q000235:genetics; D015220:Calcium Channels / Q000235:genetics; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D004252:DNA Mutational Analysis; D005091:Exons; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D006639:Histidine / Q000235:genetics; D006801:Humans; D007494:Ireland; D008297:Male; D020325:Migraine with Aura / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D020864:Calcium Channels, N-Type
chemical_list: D001224:Aspartic Acid; D015220:Calcium Channels; D006639:Histidine; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D000254:Sodium-Potassium-Exchanging ATPase; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type; C568242:SCN1A protein, human; C498531:ATP1A2 protein, human