Clinical concepts of Duchenne muscular dystrophy. The impact of molecular genetics.

Molecular genetics has transformed clinical concepts of Duchenne muscular dystrophy (DMD) in several different ways. (1) The disease can now be defined as a myopathy due to mutation at Xp21, a specific locus on the short arm of the X chromosome. (2) As a consequence of that discovery, any myopathy due to mutation at Xp21 should be a variant of DMD and should affect the same gene product. Moreover, any myopathy due to mutation at a location other than Xp21 should affect some other gene product. (3) For these reasons, DNA analysis is now needed for clinical diagnosis of muscle disease. (4) Xp21 myopathies may be mild or severe, may occur in females even though X-linked, and may be manifest only by high serum levels of creatine kinase. (5) Mental retardation is not consistently related to diseases that are encoded at Xp21. The association of mental retardation with DMD may be due to mutation in a separate gene near that for DMD. Concepts may soon be altered again as we learn about the affected gene product (dystrophin) and its role in these diseases.