title: Mutation analysis of the CACNA1A calcium channel subunit gene in 27 patients with sporadic hemiplegic migraine.
abstract: BACKGROUND
  Familial hemiplegic migraine is a rare autosomal dominant subtype of migraine with aura that in half of the families is caused by mutations in the CACNA1A gene on chromosome 19p13. In sporadic hemiplegic migraine (SHM), that is, hemiplegic migraine without affected family members, the contribution of the CACNA1A gene is unknown.
  
  
  OBJECTIVE
  To investigate the involvement of the CACNA1A calcium channel subunit gene in SHM.
  
  
  METHODS
  We screened 27 patients with SHM for mutations in the CACNA1A gene by a combination of single-strand conformational polymorphism analysis and sequence analysis.
  
  
  RESULTS
  One patient with SHM also had ataxia, nystagmus, and cerebellar atrophy on computed tomography and carried a T666M mutation. Another patient with SHM who had no cerebellar signs carried an R583Q mutation. No mutations or interictal neurological abnormalities were found in the remaining 25 patients with SHM.
  
  
  CONCLUSIONS
  Most patients with SHM do not have a CACNA1A mutation. The results of this study, combined with the findings reported in the literature, show that the presence of cerebellar symptoms in addition to the hemiplegic attacks increases the chance of finding a CACNA1A mutation. In addition, to our knowledge, we have found a first patient with SHM without cerebellar signs with a mutation.
authors.affiliation: Department of Neurology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, the Netherlands.
authors.forename: Gisela
authors.initials: G
authors.lastname: Terwindt
authors.forename: Esther
authors.initials: E
authors.lastname: Kors
authors.forename: Joost
authors.initials: J
authors.lastname: Haan
authors.forename: Frans
authors.initials: F
authors.lastname: Vermeulen
authors.forename: Arn
authors.initials: A
authors.lastname: Van den Maagdenberg
authors.forename: Rune
authors.initials: R
authors.lastname: Frants
authors.forename: Michel
authors.initials: M
authors.lastname: Ferrari
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015220:Calcium Channels / Q000235:genetics*; D002524:Cerebellar Ataxia / Q000235:genetics / Q000503:physiopathology; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020325:Migraine with Aura / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type