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Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats

Nature Genetics volume 14, pages 285–291 (1996)Cite this article

Abstract

Two forms of the neurodegenerative disorder spinocerebellar ataxia are known to be caused by the expansion of a CAG (polyglutamine) trinucleotide repeat. By screening cDNA expression libraries, using an antibody specific for polyglutamine repeats, we identified six novel genes containing CAG stretches. One of them is mutated in patients with spinocerebellar ataxia linked to chromosome 12q (SCA2). This gene shows ubiquitous expression and encodes a protein of unknown function. Normal SCA2 alleles (17 to 29 CAG repeats) contain one to three CAAs in the repeat. Mutated alleles (37 to 50 repeats) appear particularly unstable, upon both paternal and maternal transmissions. The sequence of three of them revealed pure CAG stretches. The steep inverse correlation between age of onset and CAG number suggests a higher sensitivity to polyglutamine length than in the other polyglutamine expansion diseases.

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Author notes

  1. Georges Imbert, Frédéric Saudou, Gaël Yvert, Didier Devys, Yvon Trottier, Jean-Marie Garnier, Chantal Weber, Jean-Louis Mandel, Gëraldine Cancel, Nacer Abbas, Alexandra Dürr, Olivier Didierjean, Giovanni Stevanin, Yves Agid & Alexis Brice

    Present address: Division of Neuroscience, Children's Hospital, Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, 02115, USA

  2. Georges Imbert, Frédéric Saudou, Gaël Yvert and Gëraldine Cancel: G.I, F.S, G.Y. & G.C. contributed equally to this work

  3. Jean-Louis Mandel: Correspondance should be addressed to J.-L.M.

Authors and Affiliations

  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS, INSERM, ULP, B.P. 163, 67404, Illkirch Cedex, C.U. de Strasbourg, France

    Georges Imbert, Frédéric Saudou, Gaël Yvert, Didier Devys, Yvon Trottier, Jean-Marie Garnier, Chantal Weber & Jean-Louis Mandel

  2. INSERM U.289, Hôpital de la Salpêtrière, 47 Bd de l'Hôpital, 75651, Paris, Cedex 13, France

    Gëraldine Cancel, Nacer Abbas, Alexandra Dürr, Olivier Didierjean, Giovanni Stevanin, Yves Agid & Alexis Brice

  3. Fédération de Neurologie, Hôpital de la Salpêtrière, 47 Bd de l'Hôpital, 75651, Paris, Cedex 13, France

    Alexandra Dürr, Giovanni Stevanin, Yves Agid & Alexis Brice

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Imbert, G., Saudou, F., Yvert, G. et al. Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats. Nat Genet 14, 285–291 (1996). https://doi.org/10.1038/ng1196-285

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