Novel point mutations in the dystrophin gene

Duchenne (DMD) and Becker (BMD) type muscular dystrophies are allelic X-linked recessive disorders caused by mutations in the gene encoding dystrophin. About 65% of the cases are caused by deletions, while 5-10% are duplications. The remaining 30% of affected individuals may have smaller mutations (point mutations or small deletions/insertions) which cannot be identified by current diagnostic screening strategies. In order to look for pathogenic small mutations in the dystrophin gene, we have screened the 18 exons located in the hot spot region of this gene through two different single strand conformation polymorphism (SSCP) conditions. Five different pathogenic mutations were identified in 6 out of 192 DMD/BMD patients without detectable deletions: 2 nonsense, 1 bp insertion, 1 bp deletion and 1 intronic. Except for the intronic change, which alters a splice site, all the others cause a premature stop codon. In addition, 8 apparently neutral changes were identified. However, interestingly, one of them was not identified in 195 normal chromosomes, although it was previously described in a DMD patient from a different population. The possibility that this mutation may be pathogenic is discussed. Except for two neutral changes, all the others are apparently here described for the first time.