Deficiency of α-Dystroglycan in Muscle–Eye–Brain Disease

• Published in: Biochemical and biophysical research communications 2002-03, Vol.291 (5), p.1283-1286
• Main Authors: Kano, Hiroki, Kobayashi, Kazuhiro, Herrmann, Ralf, Tachikawa, Masaji, Manya, Hiroshi, Nishino, Ichizo, Nonaka, Ikuya, Straub, Volker, Talim, Beril, Voit, Thomas, Topaloglu, Haluk, Endo, Tamao, Yoshikawa, Hideki, Toda, Tatsushi
• Format: Article
• Language: English
• Subjects: a-Dystroglycan; Child; Child, Preschool; Cytoskeletal Proteins - deficiency; Cytoskeletal Proteins - metabolism; dystroglycan; Dystroglycans; glycosylation; Humans; Immunohistochemistry; Infant; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - metabolism; Muscle, Skeletal - metabolism; Muscle-eye-brain disease; Muscular Dystrophies - metabolism; muscular dystrophy; Myopia - metabolism; N-Acetylglucosaminyltransferases - metabolism; neuronal migration disorder; O-linked mannose ^b1,2-N-acetylglucosaminyltransferase; POMGnT1; POMGnT1 gene
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2002.6608

α-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 β1,2-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 α-dystroglycan. Here we report a selective deficiency of α-dystroglycan in MEB patients. This finding suggests that α-dystroglycan is a potential target of POMGnT1 and that altered glycosylation of α-dystroglycan may play a critical role in the pathomechanism of MEB and some forms of muscular dystrophy.