Article Text

Download PDFPDF
Original article
Replacement of the myotonic dystrophy type 1 CTG repeat with ‘non-CTG repeat’ insertions in specific tissues


Background Recently, curious mutations have been reported to occur within the (CTG)n repeat tract of the myotonic dystrophy type 1 (DM1) locus. For example, the repeat, long presumed to be a pure repeat sequence, has now been revealed to often contain interruption motifs in a proportion of cases with expansions. Similarly, a few de novo somatic CTG expansions have been reported to arise from non-expanded DM1 alleles with 5–37 units, thought to be genetically stable.

Aims and methods This study has characterised a novel mutation configuration at the DM1 CTG repeat that arose as somatic mosaicism in a juvenile onset DM1 patient with a non-expanded allele of (CTG)12 and tissue specific expansions ranging from (CTG)1100 to 6000.

Results The mutation configuration replaced the CTG tract with a non-CTG repeat insertion of 43 or 60 nucleotides, precisely placed in the position of the CTG tract with proper flanking sequences. The inserts appeared to arise from a longer human sequence on chromosome 4q12, and may have arisen through DNA structure mediated somatic inter-gene recombination or replication/repair template switching errors. De novo insertions were detected in cerebral cortex and skeletal muscle, but not in heart or liver. Repeat tracts with −1 or −2 CTG units were also detected in cerebellum, which may have arisen by contractions of the short (CTG)12 allele.

Conclusion This non-CTG configuration expands current understanding of the sequence variations that can arise at this hypermutable site.

  • Myotonic dystrophy
  • non-CTG repeat
  • de novo mutation
  • insertions trinucleotide repeats
  • genetics
  • clinical genetics
  • molecular genetics
  • muscle disease
  • neuromuscular disease

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.