Origin of the expansion mutation in myotonic dystrophy

Nat Genet. 1993 May;4(1):72-6. doi: 10.1038/ng0593-72.


Myotonic dystrophy (DM) is caused by the expansion of a CTG trinucleotide repeat. The mutation is in complete linkage disequilibrium with a nearly 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 an allele 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Base Sequence
  • Biological Evolution
  • Chromosomes, Human, Pair 19*
  • European Continental Ancestry Group / genetics
  • Fragile X Syndrome / genetics
  • Genetic Markers
  • Haplotypes / genetics
  • Humans
  • Incidence
  • Linkage Disequilibrium
  • Models, Genetic
  • Molecular Sequence Data
  • Muscular Atrophy, Spinal / genetics
  • Mutation*
  • Myotonic Dystrophy / epidemiology
  • Myotonic Dystrophy / genetics*
  • Polymorphism, Genetic
  • Repetitive Sequences, Nucleic Acid*
  • Sequence Deletion


  • Genetic Markers