Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The GlcNAc(beta)1,2Man(alpha)- moiety can be synthesized by at least two mammalian glycosyltransferases, UDP-GlcNAc:alpha-3-D-mannoside beta1,2-N-acetylglucosaminyltransferase I (GnT I, EC 2.4.1.101) and UDP-GlcNAc:alpha-D-mannoside beta1,2-N-acetylglucosaminyltransferase I.2 (GnT I.2). GnT I adds a GlcNAc residue in beta1,2 glycosidic linkage to the Man(alpha)1,3 arm of the N-glycan core to initiate the biosynthesis of hybrid and complex N-glycans. GnT I.2 can add GlcNAc in beta1,2 linkage to any alpha-linked terminal Man residue but has a strong preference for the Man(alpha)1-O-Thr- moiety which occurs in alpha-dystroglycan and other O-mannosylated glycoproteins. Mouse embryos lacking a functional GnT I gene (MgatI) were unable to synthesize complex N-glycans and none survived past 10.5 days after fertilization. The embryos showed multisystemic defects in various morphogenic processes such as neural tube formation, vascularization and the determination of left-right body plan asymmetry. Six human patients with muscle-eye-brain disease (MEB) were recently shown to have point mutations in the gene encoding GnT I.2 (MGATI.2). MEB is an autosomal recessive disease characterized by congenital muscular dystrophy, ocular abnormalities, brain malformations and other multisystemic defects. Both the MGATI.2 gene and MEB disease have been mapped to chromosome 1p32-p34. At least one of the biochemical sites affected by the MGATI.2 mutations is probably the interaction between laminin in the extracellular matrix and the peripheral membrane glycoprotein alpha-dystroglycan since this interaction is believed to require the presence of the sialyl(alpha)2,3Gal(beta)1,4GlcNAc(beta)1,2Man(alpha)1-O-Ser/Thr moiety on alpha-dystroglycan. It can be concluded that the GlcNAc(beta)1,2Man(alpha)- moiety is important for mammalian development due to an essential role in two distinct biochemical pathways.
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PMID:The role of the GlcNAc(beta)1,2Man(alpha)- moiety in mammalian development. Null mutations of the genes encoding UDP-N-acetylglucosamine:alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I and UDP-N-acetylglucosamine:alpha-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I.2 cause embryonic lethality and congenital muscular dystrophy in mice and men, respectively. 1241 11

Most proteins within living organisms contain glycans. Glycan structures can modulate the biological properties and function of glycoproteins. Developments in glycobiology have revealed a new type of glycosidic linkage to the peptide portion, the O-mannosyl linkage in mammals, although heretofore it had been thought to be specific to yeast. One of the best known O-mannosyl-modified glycoproteins is dystroglycan, which is a central component of dystrophinglycoprotein complex isolated from skeletal muscle membranes. We identify and characterize a glycosyltransferase, UDP-N-acetylglucosamine: protein O-mannose beta 1,2-N-acetylglucosaminyltransferase (POMGnT1), involved in the biosynthesis of mammalian type O-mannosyl glycans. Finally, we find that the POMGnT1 gene is responsible for muscle-eye-brain disease (MEB). MEB is an autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities and brain malformation (type II lissencephaly). Like MEB, recent data suggest that the aberrant protein glycosylation of a specific glycoprotein, alpha-dystroglycan, is the primary cause of some forms of congenital muscular dystrophy. Here I review the new insight into glycobiology of muscular dystrophy and neuronal migration disorder.
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PMID:[Finding of O-mannosyl glycan in mammals and congenital muscular dystrophies due to glycosylation defects]. 1457 28

Mammalian cells produce many glycoproteins, i.e., proteins with covalently attached sugar chains. Recent advances in glycobiology have revealed the importance of sugar chains as biosignals for multi-cellular organisms including cell-cell communication, intracellular signaling, protein folding, and targeting of proteins within cells. The O-mannosyl linkage, which used to be considered specific to yeast, has recently been found in mammals. One of the best known O-mannosyl-modified glycoproteins is alpha-dystroglycan, which is a central component of the dystrophin-glycoprotein complex isolated from skeletal muscle membranes. We have identified and characterized a glycosyltransferase, UDP-N-acetylglucosamine: protein O-mannose beta1,2-N-acetylglucosaminyltransferase (POMGnT1), involved in the biosynthesis of O-mannosyl glycans. We subsequently found that loss of function of the POMGnT1 gene is responsible for muscle-eye-brain disease (MEB). MEB is an autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities and brain malformation (type II lissencephaly). Moreover, recent data suggest that aberrant protein glycosylation of alpha-dystroglycan is the primary cause of some forms of congenital muscular dystrophy. Here we review new insights into the glycobiology of muscular dystrophy and neuronal migration disorder.
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PMID:Glycosylation in congenital muscular dystrophies. 1464 63