title: The genetic and molecular basis of muscular dystrophy: roles of cell-matrix linkage in the pathogenesis.
abstract: Muscular dystrophies are a heterogeneous group of genetic disorders. In addition to genetic information, a combination of various approaches such as the use of genetic animal models, muscle cell biology, and biochemistry has contributed to improving the understanding of the molecular basis of muscular dystrophy's etiology. Several lines of evidence confirm that the structural linkage between the muscle extracellular matrix and the cytoskeleton is crucial to prevent the progression of muscular dystrophy. The dystrophin-glycoprotein complex links the extracellular matrix to the cytoskeleton, and mutations in the component of this complex cause Duchenne-type or limb-girdle-type muscular dystrophy. Mutations in laminin or collagen VI, muscle matrix proteins, are known to cause a congenital type of muscular dystrophy. Moreover, it is not only the primary genetic defects in the structural or matrix proteins, but also the primary mutations of enzymes involved in the protein glycosylation pathway that are now recognized to disrupt the matrix-cell interaction in a certain group of muscular dystrophies. This group of diseases is caused by the secondary functional defects of dystroglycan, a transmembrane matrix receptor. This review considers recent advances in understanding the molecular pathogenesis of muscular dystrophies that can be caused by the disruption of the cell-matrix linkage.
authors.affiliation: Division of Clinical Genetics, Department of Medical Genetics, Osaka University Graduate School of Medicine, 2-2-B9, Yamadaoka, Suita, 565-0871, Japan.
authors.forename: Motoi
authors.initials: M
authors.lastname: Kanagawa
authors.affiliation: Division of Clinical Genetics, Department of Medical Genetics, Osaka University Graduate School of Medicine, 2-2-B9, Yamadaoka, Suita, 565-0871, Japan. toda@clgene.med.osaka-u.ac.jp.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
mesh_terms: D000818:Animals; D019070:Cell Lineage; D049030:Dystroglycans / Q000378:metabolism; D016189:Dystrophin / Q000378:metabolism; D005109:Extracellular Matrix; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology*; D009154:Mutation
chemical_list: D016189:Dystrophin; D006023:Glycoproteins; D049030:Dystroglycans