title: Congenital muscular dystrophies involving the O-mannose pathway.
abstract: A number of forms of congenital muscular dystrophy (CMD) have been identified that involve defects in the glycosylation of dystroglycan with O-mannosyl-linked glycans. There are at least six genes that can affect this type of glycosylation, and defects in these genes give rise to disorders that have many aspects of muscle and brain pathology in common. Overexpression of one gene implicated in CMD, LARGE, was recently shown to increase dystroglycan glycosylation and restore its function in cells taken from CMD patients. Overexpression of Galgt2, a glycosyltransferase not implicated in CMD, also alters dystroglycan glycosylation and inhibits muscular dystrophy in a mouse model of Duchenne muscular dystrophy. These findings suggest that a common approach to therapy in muscular dystrophies may be to increase the glycosylation of dystroglycan with particular glycan structures.
authors.affiliation: Columbus Children's Research Institute, Department of Pediatrics, Ohio State University, 700 Children's Drive, Columbus, OH 43205, USA. MartinPT@pediatrics.ohio-state.edu
authors.forename: Paul T
authors.initials: PT
authors.lastname: Martin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism*; D005700:Galactosyltransferases / Q000096:biosynthesis* / Q000235:genetics; D006031:Glycosylation; D006801:Humans; D008358:Mannose / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020388:Muscular Dystrophy, Duchenne / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis* / Q000235:genetics; D046188:Protein Modification, Translational / Q000235:genetics
chemical_list: D049030:Dystroglycans; D005700:Galactosyltransferases; C117674:LARGE1 protein, human; C502747:Large1 protein, mouse; D017351:N-Acetylglucosaminyltransferases; C023235:glucosylceramide beta-1-4-galactosyltransferase; D008358:Mannose