Nature Genetics
4, 72 - 76 (1993)
doi:10.1038/ng0593-72
Origin of the expansion mutation in myotonic dystrophyGeorges Imbert1, Christine Kretz1, Keith Johnson2
& Jean-Louis Mandel1
1Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de l'INSERM, Faculté de Médecine et CHRU, 11 rue Humann, 67085 Strasbourg Cedex, France
2Department of Anatomy, Charing Cross and Westminster Medical School Fulham Palace Road, London W6 8RF, UK Correspondence should be addressed to J-L.M. 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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