Application of Molecular Methodologies in Muscular Dystrophies

The term “muscular dystrophy” (MD) describes a group of primary genetic disorders of muscle that often have a distinctive and recognizable clinical phenotype, accompanied by characteristic, but frequently not pathognemonic, pathological features. Research into the molecular basis of the MDs by a combination of positional cloning and candidate gene analysis has provided the basis for a reclassification of these disorders, with genetic and protein data augmenting traditional clinically based nomenclature (Table 1 ). These findings have brought insights into the molecular pathogenesis of MD, with an increasing number of potential pathways involved in arriving at a dystrophic phenotype. Some common themes can be recognized, however, including the involvement of five members of the dystrophin-associated complex (dystrophin and four sarcoglycans) in different types of MD (Fig. 1 : 1 ), and the involvement of two nuclear envelope proteins in producing an Emery-Dreifuss MD phenotype (2 ). Other disease-associated genes appear to cause MD in a completely unrelated way, such as the involvement of calpain 3 in a form of limbgirdle muscular dystrophy (3 ).