Etiology and pathogenesis of the muscular dystrophies.
Despite intensive research efforts, the cause of the muscular dystrophies has remained elusive for many decades. In the late 1980s, major advances in molecular genetics have led to the discovery of the dystrophin gene and its protein product, dystrophin. Mutations in the dystrophin gene result in dystrophin deficiency, which constitutes the pathogenetic basis of Duchenne and Becker muscular dystrophy. This major breakthrough set the scene for the ongoing discovery of the molecular basis of the muscular dystrophies. Several muscular dystrophies are caused by mutations in specific genes, which lead to deficiency of structural proteins of the sarcolemma other than dystrophin and to enzymatic dysfunction. Other muscular dystrophies have been mapped to different chromosomal loci, and in most of them, the identification of the molecular defect is ongoing. The elucidation of the molecular basis of the muscular dystrophies has a major impact on the understanding of their pathogenetic mechanisms, their nosological classification, their diagnosis and prevention, and, for the first time, offers perspectives for the development of causal treatment strategies.
D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D002882:Chromosomes, Human, Pair 13; D003598:Cytoskeletal Proteins / Q000235:genetics; D016189:Dystrophin / Q000172:deficiency / Q000235:genetics; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008565:Membrane Proteins; D009136:Muscular Dystrophies / Q000145:classification / Q000209:etiology* / Q000235:genetics; D009223:Myotonic Dystrophy / Q000235:genetics; D010641:Phenotype; D017354:Point Mutation; D049411:Utrophin
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008565:Membrane Proteins; D049411:Utrophin