Intergenerational instability of the expanded CTG repeat in the DMPK gene: studies in human gametes and preimplantation embryos

Am J Hum Genet. 2004 Aug;75(2):325-9. doi: 10.1086/422762. Epub 2004 Jun 7.


The CTG repeat at the 3' untranslated region of the dystrophia myotonica protein kinase (DMPK) gene shows marked intergenerational and somatic instability in patients with myotonic dystrophy (DM1), when the repeat is expanded to more than approximately 55 repeats. Intensive research has yielded some insights into the timing and mechanism of these intergenerational changes: (1) increases in expansion sizes occur during gametogenesis but probably not during meiosis, (2) the marked somatic mosaicism becomes apparent from the 2nd trimester of development onward and increases during adult life, and (3) DNA repair mechanisms are involved. We have performed preimplantation genetic diagnosis for DM1 since 1995, which has given us the unique opportunity to study the expanded CTG repeat in affected embryos and in gametes from affected patients. We were able to demonstrate significant increases in the number of repeats in embryos from female patients with DM1 and in their immature and mature oocytes, whereas, in spermatozoa and embryos from male patients with DM1, smaller increases were detected. These data are in concordance with data on other tissues from adults and fetuses and fill a gap in our knowledge of the behavior of CTG triplet expansions in DM1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blastocyst / enzymology*
  • Female
  • Genomic Instability
  • Germ Cells / enzymology*
  • Humans
  • Male
  • Myotonic Dystrophy / enzymology
  • Myotonic Dystrophy / genetics*
  • Protein Kinases / genetics*
  • Trinucleotide Repeat Expansion*


  • Protein Kinases