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.