Referenced in: none

Automatically associated channels: SK3 , Slo1

Title: Association of moderate polyglutamine tract expansions in the slow calcium-activated potassium channel type 3 with ataxia.

Authors: K P Figueroa, P Chan, L Schöls, C Tanner, O Riess, S L Perlman, D H Geschwind, S M Pulst

Journal, date & volume: Arch. Neurol., 2001 Oct , 58, 1649-53

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11594924

Abstract
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.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.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.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).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.