A Study on the Diagnosis of Duchenne Muscular Dystrophy

Hwang, G E; Cho, Y H; Shim, S H; Choi, B Y; Cha, B H; Hwang, Y Y; Chung, S R; Choi, S K; Kim, Y J

Abstract

Dystrophin associated muscular dystrophies [dystrophinopathies] range from the severe Duchenne to the milder Becker muscular dystrophy [DMD and BMD]. Mapping and molecular genetic studies indicate that both are the result of mutations in the huge gene that encodes dystrophin. Approximately two-thirds of the mutations in both forms are deletions of one or many exons in the dystrophin gene. This study was performed in order to establish an diagnostic strategy for dystrophinopathy. In this study muscle biopsies were taken from the clinically suspected DMD and BMD patients, and immunohistochemical staining and Western blotting with anti-dystrophin antibodies were applied to the biopsy specimens. Also, the deletion analyses with multiplex PCRs for the 18 deletion prone exons, and linkage analyses for the diagnosis of carrier status and prenatal diagnosis were performed. We suggest that the following diagnostic strategy would be useful for the genetic counseling on dystrophinpathy families. 1. First of all clinically suspected dystrophinopathy patient should be subjected to deletion analysis with multiplex PCRs. If any deletions were found, the confirmatory diagnosis and prenatal diagnosis is possible. But the carrier diagnosis should be made with linkage analysis. 2. In the cases with no deletions, a muscle biopsy should be taken from the patient and protein study with immunohistochemistry or Western blotting should be performed. With normal dystrophin pattern, consider other neuromuscular diseases other than dystrophinopathy. If dystrophin is of reduced or increased size, with or without reduction in the amount of dystrophin, BMD should be suspected. If dystrophin is absent, DMD should be suspected. In this case prenatal and carrier diagnosis should be performed with linkage analysis.