Nature Genetics
6, 14 - 18 (1994)
doi:10.1038/ng0194-14
Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12pS. Nagafuchi1, H. Yanagisawa1, K. Sato1, T. Shirayama1, E. Ohsaki1, 2, M. Bundo1, 2, T. Takeda1, 2, K. Tadokoro1, I. Kondo3, N. Murayama3, Y. Tanaka3, H. Kikushima4, K. Umino4, H. Kurosawa4, T. Furukawa4, K. Nihei5, T. Inoue2, A. Sano6, O. Komure7, M. Takahashi8, T. Yoshizawa9, I. Kanazawa10
& M. Yamada1
1National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo 154, Japan
2Laboratory of Nucleic Acid Science, Nihon University, Fuhisawa 252, Japan
3Department of Hygiene, Ehime University School of Medicine, Ehime 791-02, Japan
4Second Department of Pediatrics, Dokkyo University School of Medicine, Mibu 321-02, Japan
5National Children's Hospital, Tokyo 154, Japan
6Department of Neuropsychiatry, Ehime University School of Medicine, Ehime 791-02, Japan
7Department of Neurology and Psychiatry, Kobe University School of Medicine, Kobe 650, Japan
8Department of Neuropsychiatry, Kochi Medical School, Kochi 783, Japan
9Department of Neurology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305, Japan
10Department of Neurology, Institute of Brain Research, University of Tokyo, Tokyo 113, Japan Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by combined systemic degeneration of the dentatofugal and pallidofugal pathways. We investigated a candidate gene and found that DRPLA patients had an expanded CAG trinucleotide repeat in a gene on the short arm of chromosome 12. The repeat size varied from 7−23 in normal individuals. In patients one allele was expanded to between 49−75 repeats or occasionally even more. Expansion was usually associated with paternal transmission and only occasionally with maternal transmission. Repeat size showed a close correlation with age of onset of symptoms and disease severity. We conclude that DRPLA is the seventh genetic disorder known to be associated with expansion of an unstable trinucleotide repeat.
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