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Karla Patricia Figueroa, MS; Piu Chan, MD, PhD; Ludger Schöls, MD; Carline Tanner, MD, PhD; Olaff Riess, MD; Susan L. Perlman, MD; Daniel H. Geschwind, MD, PhD; Stefan M. Pulst, MD

Arch Neurol. 2001;58:1649-1653.

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 1 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.

Objectives  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 ² analysis (P<.001).

Conclusion  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.

From the Rose Moss Laboratory for Parkinson's and Neurodegenerative Diseases, Cedars-Sinai Medical Center Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, Calif (Ms Figueroa and Dr Pulst); the Parkinson Institute, Sunnyvale, Calif (Drs Chan and Tanner); the Department of Neurology, St Josef Hospital, Ruhr University Bochum, Bochum, Germany (Dr Schöls); the Department of Medical Genetics, Children's Hospital, University of Rostock, Rostock, Germany (Dr Riess); the Department of Neurology, University of California Medical School, Los Angeles (Drs Perlman and Geschwind); and the Division of Neurology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles (Dr Pulst).

Corresponding author: Stefan M. Pulst, Division of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (e-mail: pulst{at}cshs.org).

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