title: Replacement of the myotonic dystrophy type 1 CTG repeat with 'non-CTG repeat' insertions in specific tissues.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  This non-CTG configuration expands current understanding of the sequence variations that can arise at this hypermutable site.
authors.affiliation: Genetics and Genome Biology, The Hospital for Sick Children, TMDT Building 101 College Street, 15th Floor, Rm 15-312 East Tower, Toronto, ON M5G 1L7, Canada.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Axford
authors.forename: Arturo
authors.initials: A
authors.lastname: López-Castel
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakamori
authors.forename: Charles A
authors.initials: CA
authors.lastname: Thornton
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Pearson
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D016254:Mutagenesis, Insertional / Q000235:genetics*; D009223:Myotonic Dystrophy / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics; D016415:Sequence Alignment; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*