Author(s): Straub V; Yoshida A; Kobayashi K; Manya H; Taniguchi K; Kano H; Mizuno M; Inazu T; Mitsuhashi H; Takahashi S; Takeuchi M; Herrmann R; Talim B; Voit T; Topaloglu H; Toda T; Endo T
Abstract: 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 beta-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.
Keywords: Amino Acid Sequence Base Sequence Blotting, Western Cell Line Cell Movement Child, Preschool Cloning, Molecular DNA Mutational Analysis Female Gene Expression Glycosyltransferases/chemistry/ genetics/ metabolism Humans Male Molecular Sequence Data Muscular Dystrophies/ enzymology/ genetics/pathology Mutagenesis, Site-Directed N-Acetylglucosaminyltransferases/chemistry/ genetics/ metabolism Pedigree Phylogeny Point Mutation/ genetics RNA, Messenger/genetics/metabolism Sequence Homology, Amino Acid Substrate Specificity