Nature Genetics
14, 269 - 276 (1996)
doi:10.1038/ng1196-269
Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2Stefan-M. Pulst1, 8, Alex Nechiporuk1, *, Tamilla Nechiporuk1, *, Suzana Gispert2, Xiao-Ning Chen7, Iscia Lopes-Cendes6, Susan Pearlman4, Sidney Starkman4, Guillermo Orozco-Diaz5, Astrid Lunkes2, Pieter DeJong3, Guy A. Rouleau6, Georg Auburger2, Julie R. Korenberg7, Carla Figueroa1
& Soodabeh Sahba1
1The Rose Moss Laboratory for Parkinson's and Neurodegenerative Diseases, CSMC Burns and Allen Research Institute, and Division of Neurology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California 90048, USA
2Department of Neurology, Heinrich-Heine Universitaet, 4000 Duesseldorf 1, Germany,
3Department of Human Genetics, Roswell Park Cancer Institute, Buffalo, New York 14263-0001, USA
4Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90069, USA
5Neurology Service, Lenin Hospital, Holguin, Cuba
6Centre for Research in Neuroscience, The Montreal General Hospital, McGill University, Montreal, Quebec, Canada
7Division of Medical Genetics, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California 90048, USA
*A.N. & T.N. contributed equally to the project
8Correspondence should be addressed to S.M.P. The gene for spinocerebellar ataxia type 2 (SCA2) has been mapped to 12q24.1. A1.1−megabase contig in the candidate region was assembled in P1 artificial chromosome and bacterial artificial chromosome clones. Using this contig, we identified a CAG trinucleotide repeat with CAA interruptions that was expanded in patients with SCA2. In contrast to other unstable trinucleotide repeats, this CAG repeat was not highly polymorphic in normal individuals. In SCA2 patients, the repeat was perfect and expanded to 36−52 repeats. The most common disease allele contained (CAG)37, one of the shortest expansions seen in a CAG expansion syndrome. The repeat occurs in the 5'−coding region of SCA2 which is a member of a novel gene family.
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