Clinical application of preimplantation diagnosis for myotonic dystrophy

Myotonic dystrophy (DM) or Steinert's disease is a progressive autosomal dominant disease characterized by increasing muscle weakness, myotonia, cataracts, and endocrine abnormalities such as diabetes and testicular atrophy. The gene for DM was cloned in 1992 and the mutation was shown to be an expanded trinucleotide (CTG) repeat. A polymerase chain reaction (PCR)-based assay was described soon after that would allow (prenatal) diagnosis of the disease. Based on these PCR assays, we have developed a method for carrying out single-cell PCR for DM. In preimplantation diagnosis, embryos obtained in vitro are checked for the presence or absence of a disease, after which only embryos shown to be free of the disease under consideration are returned to the mother. A single-cell assay was developed for preimplantation diagnosis in couples where one of the parents is afflicted with DM. Twenty intracytoplasmic sperm injection (ICSI) cycles were carried out in eight patients and between one and four embryos were replaced in 17 out of 20 cycles. Two of the patients became pregnant and have had prenatal diagnosis which has confirmed that they are unaffected.