Genetic medicine and the muscular dystrophies: triumphs and tribulations

Abstract

Identification of the biochemical deficiency that causes Duchenne muscular dystrophy (DMD) has often been hailed as the beginning of the era of ‘genetic medicine’. Identification of this first ‘positionally cloned’ gene led to subsequent identification of dystrophin deficiency in muscles, the definition of a plethora of related muscular dystrophies and multiple species of genetically and biochemically identical animal models, and the publication of thousands of papers on dystrophin, the membrane cytoskeleton of myofibers, and molecular diagnostics. The recent advent of genome-wide approaches (single nucleotide polymorphisms, and microarrays) are quickly adding new insights into the molecular pathophysiology and underlying clinical progression of the dystrophies.