title: Association of moderate polyglutamine tract expansions in the slow calcium-activated potassium channel type 3 with ataxia.
abstract: BACKGROUND
  The small-conductance calcium-activated potassium channel gene (hSKCa3) contains 2 CAG repeats, 1 of which is highly polymorphic. Although this repeat is not pathologically expanded in patients with schizophrenia, some studies have suggested an allelic association with schizophrenia. CAG expansions in other genes such as the alpha1 subunit of a brain-specific P/Q-type calcium channel gene cause spinocerebellar ataxia type 6, whereas the length of the CAG repeat in the RAI1 gene modifies the age of onset of spinocerebellar ataxia type 2.
  
  
  OBJECTIVE
  To evaluate expansions in the hSKCa3 polyglutamine domain as causative for ataxia, and to study the association between the length of the polyglutamine repeat and the presence of ataxia.
  
  
  METHODS
  We analyzed this repeat in 122 patients with autosomal dominant cerebellar ataxia, or sporadic ataxia, and compared allele distribution with 750 alleles seen in 2 healthy control groups and 172 alleles in patients with Parkinson disease.
  
  
  RESULTS
  The distribution of alleles in ataxia patients and controls was significantly different by Wilcoxon rank test (P <.001). Twenty-two or more polyglutamine tracts were more common in ataxia patients compared with controls by chi2 analysis (P<.001).
  
  
  CONCLUSIONS
  Longer stretches of polyglutamines in a human potassium channel are not causative for ataxia, but they are associated with the presence of ataxia. There is no association with the presence of Parkinson disease.
authors.affiliation: Division of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. pulst@cshs.org
authors.forename: K P
authors.initials: KP
authors.lastname: Figueroa
authors.forename: P
authors.initials: P
authors.lastname: Chan
authors.forename: L
authors.initials: L
authors.lastname: Schöls
authors.forename: C
authors.initials: C
authors.lastname: Tanner
authors.forename: O
authors.initials: O
authors.lastname: Riess
authors.forename: S L
authors.initials: SL
authors.lastname: Perlman
authors.forename: D H
authors.initials: DH
authors.lastname: Geschwind
authors.forename: S M
authors.initials: SM
authors.lastname: Pulst
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001259:Ataxia / Q000235:genetics*; D001483:Base Sequence; D001921:Brain / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000235:genetics; D010455:Peptides / Q000235:genetics*; D011110:Polymorphism, Genetic; D015221:Potassium Channels / Q000235:genetics*; D024681:Potassium Channels, Calcium-Activated; D012016:Reference Values; D012559:Schizophrenia / Q000235:genetics; D051640:Small-Conductance Calcium-Activated Potassium Channels; D020754:Spinocerebellar Ataxias / Q000145:classification / Q000235:genetics*; D018454:Spouses; D018911:Trinucleotide Repeats
chemical_list: C406328:KCNN3 protein, human; D010455:Peptides; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; C097188:polyglutamine