Myotonic dystrophy is the commonest autosomal dominant type of muscular dystrophy in adults. It is one of the trinucleotide repeat expansion disorders, and its severity correlates with the number of CTG repeats in the myotonic dystrophy gene. It has been suggested that myotonic dystrophy exhibits the phenomenon of preferential transmission of the larger mutated alleles that has been described in other trinucleotide repeat disorders. Several authors have reported that the frequency of transmission of the mutated alleles is higher than 50%--a finding that, if true, does not comply with the Mendelian laws of segregation. However, these studies were based on data from the analysis of pedigrees with ascertainment bias. In our study, we determined the frequency of transmission of mutated alleles using data from prenatal molecular studies, which are not subject to ascertainment bias. This is the first study to examine the segregation of the mutated alleles in myotonic dystrophy in pregnancy. Eighty-three fetuses were examined, 30 of 62 mothers (48.38%) and 8 of 21 fathers (38.09%) transmitted the mutated allele, giving an overall transmission rate of 45.78%. We found no evidence of statistically significant deviation of the frequency of transmission of the mutated alleles from the 50% expected in autosomal dominant disorders. This study, unlike previous ones, excludes preferential transmission in myotonic dystrophy, a finding that may be attributable to the lack of correction for ascertainment bias in previous studies and to the use of prenatal data in this study.
Copyright 2004 Wiley-Liss, Inc.