Point Mutation Detection in the Dystrophin Gene

Patients with Duchenne and Becker muscular dystrophy (DMD/BMD) carry mutations in the dystrophin gene. To date, the dystrophin gene is the largest gene ever found in a living organism, measuring 2.4 Mb (1 –3 ). The major muscle transcript consists of 79 exons, spliced together in a 14-kb mature RNA (1 ,2 ). The protein coding region spans 11,058 bp, and encodes a 3685 amino acid protein with a mol wt of 427 kDa (2 ). Transcripts have been identified in many nonmuscular tissues, initiated from eight different promoters, some of which are tissue-specific. Extensive alternative splicing, especially toward the 3′ end of the gene (i.e., exons 70–78), produces a range of slightly shorter transcripts. The gene thus encodes a very complex set of protein isoforms, of which the major constituents have been designated Dp427m (muscle), Dp427c (cortical), Dp427p (Purkinje cells), Dp260 (retina), Dp140 (central nervous system), Dp116 (peripheral nerve), Dp71, and Dp40 (4 ).