HETERODUPLEX ANALYSIS OF THE DYSTROPHIN GENE - APPLICATION TO POINT MUTATION AND CARRIER DETECTION

Approximately one-third of the Duchenne muscular dystrophy patients ha ve undefined mutations in the dystrophin gene. For carrier and prenata l studies in families without detectable mutations, the indirect restr iction fragment length polymorphism linkage approach is used. Using a multiplex amplification and heteroduplex analysis of dystrophin exons, we identified nonsense mutations in two DMD patients. Although the no nsense mutations are predicted to severely truncate the dystrophin pro tein, both patients presented with mild clinical courses of the diseas e. As a result of identifying the mutation in the affected boys, direc t carrier studies by heteroduplex analysis were extended to other rela tives. We conclude that the technique is not only ideal for mutation d etection but is also useful for diagnostic testing. (C) 1994 Wiley-Lis s, Inc.