The Wellcome Lecture, 1988 - Muscular dystrophy: a time of hope

Duchenne muscular dystrophy (DMD) and its less severe allele Becker muscular dystrophy (BMD) are progressive muscle-wasting disorders of children, DMD is characterized by rapid loss of muscle fibres and the ensuing weakness results in lost mobility and eventual premature death. Despite extensive research for many years, the basic underlying biochemical defect has remained elusive. Here I try to demonstrate how the powerful techniques of molecular genetics can be used to gain a further understanding of this particular disorder and how, in principle, the techniques can be applied to the other 3000 human genetic disorders that are so far uncharacterized. Once the chromosomal map position of DMD was established, the locus that was being disrupted by mutation could be identified and the encoded protein product predicted from the nucleotide sequence of the RNA transcript. This has led to the identification of a previously uncharacterized protein named dystrophin. As the normal function of dystrophin is determined, more accurate clinical diagnosis of DMD and BMD should result and potential approaches to therapy should be designed.