A molecular survey of Israeli Duchenne and Becker muscular dystrophy patients

Duchenne (DMD) and Becker (BMD) muscular dystrophy are allelic X-linked recessive diseases caused by a mutation in the dystrophin gene located on the short arm of chromosome X (Xp21). The dystrophin gene is the largest gene known in humans, extending over 2300 kb and containing more than 70 exons coding for a 420 KD protein comprising 3685 amino acids. The gene is highly unstable, with a high percentage of deletions and rearrangements. A third of dystrophin mutations are new mutations. The frequency of DMD is 1:3500 liveborn males, and that of BMD 1:10000. These dystrophies are severe, progressive, and lethal. BMD/DMD patients and 2/3 of female carriers have high levels of creatine phosphokinase (CK). During the past 5 years, 169 families with patients affected by progressive muscular dystrophy were examined and counselled. We were able to exclude the diagnosis of DMD/BMD in 49 families on the basis of clinical symptoms and signs, normal dystrophin on biopsy (11 families) and/or the absence of linkage to chromosome X by analysis of RFLP derived haplotypes. Molecular analysis was performed on 111 DMD/BMD families (five BMD and 106 DMD) with 81 available probands. This study resulted in the establishment in Israel of an integrated diagnostic protocol for DMD/BMD, employing genetic, biochemical and molecular techniques. Molecular analysis provided most of the families with new and essential information.