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Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p

Nature Genetics volume 6, pages 14–18 (1994)Cite this article

Abstract

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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Authors and Affiliations

  1. National Children's Medical Research Center, 3-35-31, Taishido, Setagaya, Tokyo, 154, Japan

    S. Nagafuchi, H. Yanagisawa, K. Sato, T. Shirayama, E. Ohsaki, M. Bundo, T. Takeda, K. Tadokoro & M. Yamada

  2. Laboratory of Nucleic Acid Science, Nihon University, Fuhisawa, 252, Japan

    E. Ohsaki, M. Bundo, T. Takeda & T. Inoue

  3. Department of Hygiene, Ehime University School of Medicine, Ehime, 791-02, Japan

    I. Kondo, N. Murayama & Y. Tanaka

  4. Second Department of Pediatrics, Dokkyo University School of Medicine, Mibu, 321-02, Japan

    H. Kikushima, K. Umino, H. Kurosawa & T. Furukawa

  5. National Children's Hospital, Tokyo, 154, Japan

    K. Nihei

  6. Department of Neuropsychiatry, Ehime University School of Medicine, Ehime, 791-02, Japan

    A. Sano

  7. Department of Neurology and Psychiatry, Kobe University School of Medicine, Kobe, 650, Japan

    O. Komure

  8. Department of Neuropsychiatry, Kochi Medical School, Kochi, 783, Japan

    M. Takahashi

  9. Department of Neurology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, 305, Japan

    T. Yoshizawa

  10. Department of Neurology, Institute of Brain Research, University of Tokyo, Tokyo, 113, Japan

    I. Kanazawa

Authors
  1. S. Nagafuchi
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  9. I. Kondo
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Nagafuchi, S., Yanagisawa, H., Sato, K. et al. Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p. Nat Genet 6, 14–18 (1994). https://doi.org/10.1038/ng0194-14

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  • DOI: https://doi.org/10.1038/ng0194-14

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