Identification of carriers of Duchenne muscular dystrophy: value of molecular analysis

Currently, molecular methods are the most accurate diagnostic tools for carrier detection and prenatal diagnosis of Duchenne muscular dystrophy (DMD). This report illustrates the value of molecular diagnosis as opposed to previous diagnostic methods, the need for frequent re-evaluations as new methodologies develop, and the necessity for in-depth genetic counseling. In Family 1, the proposita was predicted to be a carrier by an indirect assay (abnormal in vitro muscle ribosomal protein synthesis). DNA analysis using restriction fragment length polymorphisms (RFLPs) indicated that she was not a carrier. She gave birth to a predicted non-affected male, who inherited the gene in question. In Family 2 the proposita, an obligate carrier, was initially evaluated by RFLP analysis. Two pregnancies were monitored by first trimester chorionic villous sampling. Re-evaluation indicated that all affected individuals, including one of the embryos, carried a deletion of the dystrophin gene. The identification of an RFLP within the region containing the deletion allowed unambiguous determination of the carrier status of all individuals.