Replacement of the myotonic dystrophy type 1 CTG repeat with 'non-CTG repeat' insertions in specific tissues. Issue 7 (27th May 2011)

• Record Type: Journal Article
• Authors: Axford, Michelle M; López-Castel, Arturo; Nakamori, Masayuki; Thornton, Charles A; Pearson, Christopher E
• Is Part Of: Journal of medical genetics. Volume 48:Issue 7(2011)
• Page Start: 438
• Page End: 443
• Publication Date: 2011-05-27
• Subjects: Myotonic dystrophy -- non-CTG repeat -- de novo mutation -- insertions trinucleotide repeats -- genetics -- clinical genetics -- molecular genetics -- muscle disease -- neuromuscular disease; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmg.2010.085944
• Languages: English
• ISSNs: 1468-6244

Abstract

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. 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.