title: Protein glycosylation: chaperone mutation in Tn syndrome.
abstract: Tn syndrome is a rare autoimmune disease in which subpopulations of blood cells in all lineages carry an incompletely glycosylated membrane glycoprotein, known as the Tn antigen. This truncated antigen has the sugar N-acetylgalactosamine alpha-linked to either a serine or threonine amino-acid residue, whereas the correct T antigen has an additional terminal galactose; the defect may be due to a malfunction of the glycosylating enzyme T-synthase. Here we show that Tn syndrome is associated with a somatic mutation in Cosmc, a gene on the X chromosome that encodes a molecular 'chaperone' that is required for the proper folding and hence full activity of T-synthase. The production of the autoimmune Tn antigen by a glycosyltransferase enzyme rendered defective by a disabled chaperone may have implications for other Tn-related disorders such as IgA nephropathy, a condition that can result in renal failure.
authors.affiliation: Department of Biochemistry and Molecular Biology, and Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
authors.forename: Tongzhong
authors.initials: T
authors.lastname: Ju
authors.forename: Richard D
authors.initials: RD
authors.lastname: Cummings
mesh_terms: D000483:Alleles; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005700:Galactosyltransferases / Q000737:chemistry / Q000378:metabolism*; D040181:Genetic Diseases, X-Linked / Q000235:genetics; D006031:Glycosylation; D006801:Humans; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D013577:Syndrome
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; C505369:C1GALT1C1 protein, human; D018832:Molecular Chaperones; C040286:Tn antigen; C505293:C1GALT1 protein, human; D005700:Galactosyltransferases