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Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the α1A-voltage-dependent calcium channel

Nature Geneticsvolume 15pages6269 (1997) | Download Citation



A polymorphic CAG repeat was identified in the human α1A voltage-dependent calcium channel subunit. To test the hypothesis that expansion of this CAG repeat could be the cause of an inherited progressive ataxia, we genotyped a large number of unrelated controls and ataxia patients. Eight unrelated patients with late onset ataxia had alleles with larger repeat numbers (21‐27) compared to the number of repeats (4‐16) in 475 non‐ataxia individuals. Analysis of the repeat length in families of the affected individuals revealed that the expansion segregated with the phenotype in every patient. We identified six isoforms of the human α1A calcium channel subunit. The CAG repeat is within the open reading frame and is predicted to encode glutamine in three of the isoforms. We conclude that a small polyglutamine expansion in the human α1A calcium channel is most likely the cause of a newly classified autosomal dominant spinocerebellar ataxia, SCA6.

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Author notes

  1. S.H. Subramony: Correspondence should be addressed to C.C.I.

  2. Cheng Chi Lee: All correspondence should be addressed to C.C.L.


  1. Departments of Molecular and Human Genetics Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA

    • Olga Zhuchenko
    • , Jennifer Bailey
    • , Penelope Bonnen
    • , David W. Stockton
    • , Huda Y. Zoghbi
    •  & Cheng Chi Lee
  2. Departments of Neurology and the Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA

    • Tetsuo Ashizawa
    •  & Huda Y. Zoghbi
  3. Veterans Affairs Medical Center and Houston, Texas, 77030, USA

    • Tetsuo Ashizawa
  4. UTMD Anderson Cancer Center, Houston, Texas, 77030, USA

    • Chris Amos
  5. Department of Neurology and Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, 55455, USA

    • William B. Dobyns
  6. University of Mississippi Medical Center, Jackson, Mississippi, 39216, USA

    • S.H. Subramony
  7. Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA

    • Huda Y. Zoghbi


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