Nature Genetics
17, 65 - 70 (1997)
doi:10.1038/ng0997-65
Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansionGilles David1, Nacer Abbas1, Giovanni Stevanin1, Alexandra Dürr1, 2, Gaël Yvert3, Géraldine Cancel1, Chantal Weber3, Georges Imbert3, Frédéric Saudou3, Eric Antoniou4, Harry Drabkin4, Robert Gemmill4, Paola Giunti5, Ali Benomar6, 7, Nick Wood5, Merle Ruberg1, Yves Agid1, 2, Jean-Louis Mandel3
& Alexis Brice1, 2
1INSERM U289, Hôpital de la Salpêtrière, 47 bd. de I'Hôpital, 75651 Paris Cedex 13, France.
2Fédération de Neurologie, Hôpital de la Salpêtrière, 47 bd. de l'Hôpital, 75651 Paris Cedex 13, France.
3Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS, INSERM, ULP, B.P. 163, 67404 Illkirch Cedex, C U. de Strasbourg, France.
4University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, Colorado 80262, USA.
5Institute of Neurology, Queen Square, London WC1N3BG, UK.
6Service de Neurologie (Prof. T. Chkili), Hôpital des Speéialtiés, Rabat, Morocco. G.D. & N.A. contributed equally to this work.
7e-mail: brice@u289.ext.infobiogen.fr. The gene for spinocerebellar ataxia 7 (SCA7) has been mapped to chromosome 3p12−13. By positional cloning, we have identified a new gene of unknown function containing a CAG repeat that is expanded in SCA7 patients. On mutated alleles, CAG repeat size is highly variable, ranging from 38 to 130 repeats, whereas on normal alleles it ranges from 7 to 17 repeats. Gonadal instability in SCA7 is greater than that observed in any of the seven known neuro-degenerative diseases caused by translated CAG repeat expansions, and is markedly associated with paternal transmissions. SCA7 is the first such disorder in which the degenerative process also affects the retina.
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