Prenatal diagnosis of congenital myotonic dystrophy in two Japanese families: direct mutation analysis by a non-radioisotope PCR method and haplotype analysis with flanking DNA markers.

The prenatal diagnosis of congenital myotonic dystrophy in two Japanese families was reported. The CTG repeat size in the myotonin/protein kinase gene was determined by a nonradioisotope PCR method. Polymorphisms of the DNA markers (ApoCII, X75b-VSSM and KLK-1) flanking the CTG repeat were analyzed from normal Japanese and were used to determine the risk haplotype. Two pregnant women with myotonic dystrophy requested prenatal diagnosis. The first case was diagnosed as having myotonic dystrophy at 36 weeks of pregnancy. The CTG repeat size in the cord blood from the fetus was not expanded and the risk for the disease was judged to be low by haplotype analysis with the X75b-VSSM marker. In the second case, the chorionic villus was sampled in the pregnant mother who had already had two children with congenital myotonic dystrophy. The small expanded allele (36 repeats) from the mother and a normal allele from the father were detected in the chorionic villus. The risk for the disease was not determined by haplotype analysis with ApoCII and X75b-VSSM, only being judged as low by haplotype analysis with KLK-1 in the second case. These babies from two families were born and developed normally. DNA diagnosis for direct CTG repeat expansion combined with haplotype analysis has been useful for pregnant women with myotonic dystrophy who are at high risk of having severely affected babies.