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 Muscular Dystrophies and Dystrophin-Glycoprotein Complex

Muscular Dystrophy (MD) refers to a family of genetic disorders including Duchenne (DMD), Becker’s (BMD), Emery-Dreifuss (EDMD), Limb-girdle (LGMD), Facioscapulohumeral (FSHD), Fukuyama congenital (FCMD), Myotonic (myoconvulsive) (MMD), Oculopharyngeal (OPD) and Congenital (CMD) muscular dystrophies and sarcoglycanopathies that affect muscles and body movement.

Various skeletal muscular dystrophies (MD) result from defects in the muscle dystrophin-glycoprotein complex (DGC) which links the sarcolemma membrane (SM) to the cytoskeleton network (through actin) and the basal lamina (through laminin, agrin, perlecan or neurexin). Components of the DGC include the intracellular (protein triplet) cytoskeleton-linking protein, dystrophin; the lamina-linking glycoprotein complex, dystroglycans (alpha (lamina-binding) and beta (SM-spanning) subunits); the SM spanning α, β, γ, and δ sarcoglycans and sarcospan; α, and β, syntrophins; and dystrobrevin.

The classicl forms of muscular dystrophy, Duchenne and Becker’s, result from mutations of the dystrophin gene and disruption of the dystrophin-glycoprotein complex. Duchenne is the more severe form. Emery- Dreifuss muscular dystrophy has been linked to the LMNA gene which encodes nuclear envelop proteins lamin A and lamin C. Limb-girdle muscular dystrophy is linked to defective glycosylation resulting from mutations of the fukutin-related protein (FKRP) gene. The cause of Facioscapulohumeral MD is not well characterized. Fukuyama congenital muscular dystrophy has been linked to mutation in the phospholigand transferase, fukutin. Myotonic muscular dystrophy (MMD) is characterized by sodium channel gating deficiencies that link to defective 3’-untranslated regions of the myotonic dystrophy protein kinase (DMPK) gene. Oculopharyngeal (OPD) is linked to mutations in the polyadenine binding protein nuclear 1 (PABPN1) gene. Congenital muscular dystrophy type 1C, has been linked to the fukutin-related protein (FKRP) gene. FCMD, Congenital MD, type IC and ID and LGMD, type 2I (dystroglycanopathies) have been linked to glycosylation disorders of dystroglycans.