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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Blotting, Western
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Cell Line
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Cell Movement*
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Child, Preschool
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Cloning, Molecular
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DNA Mutational Analysis
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Female
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Gene Expression
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Glycosyltransferases / chemistry
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Glycosyltransferases / genetics*
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Glycosyltransferases / metabolism*
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Humans
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Male
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Molecular Sequence Data
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Muscular Dystrophies / enzymology*
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Muscular Dystrophies / genetics*
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Muscular Dystrophies / pathology
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Mutagenesis, Site-Directed
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N-Acetylglucosaminyltransferases / chemistry
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N-Acetylglucosaminyltransferases / genetics*
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N-Acetylglucosaminyltransferases / metabolism*
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Pedigree
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Phylogeny
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Point Mutation / genetics*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Sequence Homology, Amino Acid
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Substrate Specificity
Substances
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RNA, Messenger
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Glycosyltransferases
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N-Acetylglucosaminyltransferases
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protein O-mannose beta-1,2-N-acetylglucosaminyltransferase