A partial deletion of the muscular dystrophy gene transmitted twice by an unaffected male.

A gene of unknown function located in band Xp21 on the short arm of the human X chromosome gives rise to X-linked recessive muscular dystrophy, of either Duchenne or Becker type, when mutated. The gene encodes a large muscle-specific transcript of about 14 kilobases (kb) and its genomic size extends over more than 1,800 kb. The high mutation rate (about 10(-4) per generation) is likely to result from the large target size. Submicroscopic deletions, detectable with one or more of the dozen cloned DNA probes available for regions within the gene, constitute a significant proportion of the mutations. Because no such deletions have been found in normal individuals, it is assumed that intragenic deletions are the molecular basis of the mutations. The origin of deletions can be traced in families. With sufficient data collected, it will soon be possible to answer questions about the relative frequencies of mutations in male and female gametogenesis and about the timing of mutational events in mitotic or meiotic stages of germ cell development. We have studied a four generation family containing males who have Duchenne muscular dystrophy due to deletion of the sequence recognized by intragenic probe J-Bir. The deletion was present in two of five daughters of a woman who herself did not have the deletion. Haplotype analysis on 15 members of this family using nine informative restriction fragment length polymorphism (RFLP) markers indicated that the J-Bir deletion chromosome was transmitted from the unaffected father.