Application of Molecular Methodologies in Muscular Dystrophies

Abstract

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).