Instability in the transmission of the myotonic dystrophy CTG repeat in human oocytes and preimplantation embryos

Objective: to elucidate the timing and variability of CTG repeat expansion within the human dystrophia Myotonica protein kinase (DMPK) gene in early development. Design: Triplet-primed polymerase chain reaction was used to amplify the expanded CTG repeat in oocytes and embryos obtained from myotonic dystrophy 1 (DMI) patients, and a heminested polymerase chain reaction approach was used to amplify the normal CTG repeats in supernumerary IVF embryos. Setting: University hospital laboratory. Patient(s): Two DMI-affected females undergoing preimplantation genetic diagnosis who carried different CTG repeats. Also, 61 IVF patients who carried a (CTG)(5-18) and (CTG)(19-37) normal DMPK repeat. Intervention(s): None. Main Outcome Measure(s): The degree of expansion of the repeat in the oocytes and embryos compared with the DM1-affected maternal repeat and the size of the (CTG)(19-37) repeat compared with the parental size in IVF embryos. Result(s):The degree of repeat expansion was greater-than the DM1 maternal lymphocyte for two of four oocytes, including a germinal vesicle-stage oocyte and 17 of 20 three-cell to blastocyst stage embryos. A change in the (CTG)(19-37) repeat was-seen in 7 (7%) of 95 paternal transmissions but in no maternal transmissions. Conclusion(s): Because the repeat was already expanded in the immature oocyte, the initial expansion most likely occurs during, oogenesis. A variable degree of DMPK(CTG), expansion in the embryo is seen from different mothers.In addition, instability in paternal transmission of normal-range (CTG)(19-37) repeats occurs at the level of the embryo.