Fukutin and Fukuyama Congenital Muscular Dystrophy
Recent genetic and biochemical studies have revealed that mutations in (putative) glycosyltransferases and subsequent abnormal glycosylation of dystroglycan are associated with several forms of congenital muscular dystrophies (Kanagawa and Toda 2006). Fukuyama congenital muscular dystrophy (FCMD), the second most common childhood muscular dystrophy in Japan, is one of the congenital muscular dystrophies displaying glycosylation defects of α-dystroglycan. The gene responsible for this disease is fukutin, and its protein product is assumed to participate in cellular glycosylation events. FCMD is characterized by severe congenital muscular dystrophy, abnormal neuronal migration associated with mental retardation and epilepsy, and frequent eye abnormalities. Therefore, fukutin-dependent glycosylation of α-dystroglycan plays crucial roles in structural/functional maintenance of skeletal muscle, central/peripheral nervous system, and eye. α-Dystroglycan, a highly glycosylated protein, forms a protein complex with β-dystroglycan, and the dystroglycan complex links laminin in the extracellular matrix to the cellular actin cytoskeleton. Abnormal glycosylation of α-dystroglycan results in a severe reduction in laminin-binding activity, and thus disruption of the interaction between dystroglycan and laminin caused by fukutin mutations is believed to be the major cause of FCMD.
KeywordsMuscular Dystrophy Congenital Muscular Dystrophy Muscle Cell Membrane Abnormal Glycosylation Muscle Plasma Membrane
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