Duchenne Muscular Dystrophy (DMD) is untreatable, severe, deteriorative and relatively common X-linked recessive disorder caused by a mutation of the structural protein dystrophin. DMD causes worsening muscle weakness, with wheelchair confinement by ∼12 years and death by ∼20 years. Females very rarely have DMD, since it is lethal in males and thus cannot be passed on to XX progeny; however, females with Turner Syndrome or X chromosome translocations have been known to have DMD. About 1/3 of DMD patients have new mutations, while 2/3 have maternal inheritance of the DMD allele.
At ∼2,300 kilobases (1.5% of the X chromosome), the gene encoding dystrophin is among the largest in the animal kingdom. It contains 79 exons, and its 7 tissue-specific promoters allow differential splicing into tissue-specific and developmentally regulated isoforms. Dystrophin is a massive complex with a myriad of functions that maintain muscle integrity. Most DMD patients have deletions in either the 5' or central regions, while most other patients have randomly distributed point mutations. Due to its sheer size, the gene for dystrophin has one of the highest frequencies of mutation.
PCR analysis of carriers and fetuses can identify deletions in dystrophin, and molecular sequencing can identify point mutations. Also, linked markers are useful for prenatal diagnosis when direct analysis does not detect a mutation. If a DMD patient is the first affected family member and a mutant dystrophin allele is not found in his mother, then most of the time it is due to a new mutation. However, ∼10% of such cases are in fact due to maternal germline mosaicism, meaning only some of her cells carry the mutant allele; this is significant due to an increased risk of recurrence.