Molecular deletions in the Duchenne/Becker muscular dystrophy gene

Abstract

To gain further information relating to the frequency, position and size of DNA deletions in the Duchenne/Becker muscular dystrophy (D/BMD) gene region, and to detect any correlation of these deletions with phenotype, a large clinic-based population of DMD and BMD patients has been investigated using 13 cloned intragenic sequences. Our of 263 separate patients studied, 75 showed a deletion of at least one locus (28.5%). These represented 25.6% (55/215) of DMD patients and 41.7% (20/48) of BMD patients, suggesting that the milder phenotype is more often likely to be due to a deletion. The deletions range from 6 kilobases (kb) to greater than 1000 kb in size. The distribution of deletions across the gene region shows at least one region (detected by P20) prone to deletion mutations in both DMD and BMD patients. There is no simple correlation of position or extent of deletions with DMD or BMD, although deletion of a specific region towards the 5' end of the gene may be more often associated with a milder phenotype. Apparently similar deletions can give rise to phenotypes differing significantly in severity, presumably indicating further complexities in the molecular or cellular pathology.