Muscular Dystrophy and Neuronal Migration Disorder Caused by Mutations in a Glycosyltransferase, POMGnT1

• Published in: Developmental cell Vol. 1; no. 5; pp. 717 - 724
• Main Authors: Yoshida, Aruto, Kobayashi, Kazuhiro, Manya, Hiroshi, Taniguchi, Kiyomi, Kano, Hiroki, Mizuno, Mamoru, Inazu, Toshiyuki, Mitsuhashi, Hideyo, Takahashi, Seiichiro, Takeuchi, Makoto, Herrmann, Ralf, Straub, Volker, Talim, Beril, Voit, Thomas, Topaloglu, Haluk, Toda, Tatsushi, Endo, Tamao
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2001
• Subjects: Amino Acid Sequence; Base Sequence; Blotting, Western; Cell Line; Cell Movement; Child, Preschool; Cloning, Molecular; DNA Mutational Analysis; Female; Gene Expression; Glycosyltransferases - chemistry; Glycosyltransferases - genetics; Glycosyltransferases - metabolism; Humans; Male; Molecular Sequence Data; Muscle-eye-brain disease; Muscular Dystrophies - enzymology; Muscular Dystrophies - genetics; Muscular Dystrophies - pathology; Mutagenesis, Site-Directed; N-Acetylglucosaminyltransferases - chemistry; N-Acetylglucosaminyltransferases - genetics; N-Acetylglucosaminyltransferases - metabolism; Pedigree; Phylogeny; Point Mutation - genetics; POMGnT1 gene; protein O-mannose ^b-1,2-N-acetylglucosaminyltransferase; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sequence Homology, Amino Acid; Substrate Specificity
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/S1534-5807(01)00070-3

Muscle-eye-brain disease (MEB) is an autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities, and lissencephaly. Mammalian O-mannosyl glycosylation is a rare type of protein modification that is observed in a limited number of glycoproteins of brain, nerve, and skeletal muscle. Here we isolated a human cDNA for protein O-mannose β-1,2- N-acetylglucosaminyltransferase (POMGnT1), which participates in O-mannosyl glycan synthesis. We also identified six independent mutations of the POMGnT1 gene in six patients with MEB. Expression of most frequent mutation revealed a great loss of the enzymatic activity. These findings suggest that interference in O-mannosyl glycosylation is a new pathomechanism for muscular dystrophy as well as neuronal migration disorder.