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Origin of the expansion mutation in myotonic dystrophy

Nature Genetics volume 4, pages 72–76 (1993)Cite this article

Abstract

Myotonic dystrophy (DM) is caused by the expansion of a CTG trinucleotide repeat. The mutation is in complete linkage disequilibrium with a nearby two–allele insertion/deletion polymorphism, suggesting a single origin for the mutation or predisposing mutation. To trace this ancestral event, we have studied the association of CTG repeat alleles in a normal population to alleles of the insertion/deletion polymorphism and of a (CA)n repeat marker 90 kilobases from the DM mutation. The results strongly suggest that the initial predisposing event(s) consisted of a transition from a (CTG)5 allele to anallele with 19 to 30 repeats. The heterogeneous class of (CTG)19–30 alleles which has an overall frequency of about 10%, may constitute a reservoir for recurrent DM mutations.

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Authors and Affiliations

  1. Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de l'INSERM, Faculté de Médecine et CHRU, 11 rue Humann, 67085, Strasbourg Cedex, France

    Georges Imbert, Christine Kretz & Jean-Louis Mandel

  2. Department of Anatomy, Charing Cross and Westminster Medical School Fulham Palace Road, London, W6 8RF, UK

    Keith Johnson

Authors
  1. Georges Imbert
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  2. Christine Kretz
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  3. Keith Johnson
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  4. Jean-Louis Mandel
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Imbert, G., Kretz, C., Johnson, K. et al. Origin of the expansion mutation in myotonic dystrophy. Nat Genet 4, 72–76 (1993). https://doi.org/10.1038/ng0593-72

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