Author(s): Straub V; Kano H; Kobayashi K; Herrmann R; Tachikawa M; Manya H; Nishino I; Nonaka I; Talim B; Voit T; Topaloglu H; Endo T; Yoshikawa H; Toda T
Abstract: Alpha-dystroglycan is a component of the dystrophin-glycoprotein-complex, which is the major mechanism of attachment between the cytoskeleton and the extracellular matrix. Muscle-eye-brain disease (MEB) is an autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities and lissencephaly. We recently found that MEB is caused by mutations in the protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase (POMGnT1) gene. POMGnT1 is a glycosylation enzyme that participates in the synthesis of O-mannosyl glycan, a modification that is rare in mammals but is known to be a laminin-binding ligand of alpha-dystroglycan. Here we report a selective deficiency of alpha-dystroglycan in MEB patients. This finding suggests that alpha-dystroglycan is a potential target of POMGnT1 and that altered glycosylation of alpha-dystroglycan may play a critical role in the pathomechanism of MEB and some forms of muscular dystrophy.
Keywords: Child Child, Preschool Cytoskeletal Proteins/deficiency/ metabolism Dystroglycans Humans Immunohistochemistry Infant Membrane Glycoproteins/deficiency/ metabolism Muscle, Skeletal/ metabolism Muscular Dystrophies/ metabolism Myopia/metabolism N-Acetylglucosaminyltransferases/metabolism