title: Galactosyltransferase I is a gene responsible for progeroid variant of Ehlers-Danlos syndrome: molecular cloning and identification of mutations.
abstract: A human cDNA encoding a novel galactosyltransferase was identified based on BLAST analysis of expressed sequence tags, and the cDNA clones were isolated, showing a type II membrane protein with 327 amino acids and 38% homology to the Caenorhabditis elegans sqv-3 gene involved in vulval invagination and oocyte development. This cDNA exhibited marked galactosyltransferase activity specific for p-nitrophenyl-beta-D-xylopyranoside, and also restored glycosaminoglycan (GAG) synthesis to galactosyltransferase I-deficient CHO mutant pgsB-761 cells. The enzyme product contained beta-1,4-linked galactosyl residues, indicating that the enzyme is galactosyltransferase I (UDP-D-galactose: D-xylose beta-1,4-D-galactosyltransferase; EC 2.4.1.133) involved in the synthesis of the GAG-protein linkage region of proteoglycans. Mutations of this gene were investigated in a case of Ehlers-Danlos syndrome (progeroid variant), since reduced activity of galactosyltransferase I had been reported in this disease by others. As expected, the patient gene contained two different mutations (A186D, L206P). The mutations showed, respectively, 10-50% and 0% of the enzyme activity compared with wild type, suggesting that galactosytransferase I (XGal-T1) is at least one of the genes responsible for Ehlers-Danlos syndrome (progeroid variant).
authors.affiliation: Department of Biochemistry II, Nagoya University School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Japan. koichi@med.nagoya-u.ac.jp
authors.forename: Koichi
authors.initials: K
authors.lastname: Furukawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Okajima
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004535:Ehlers-Danlos Syndrome / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D005700:Galactosyltransferases / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D013577:Syndrome
chemical_list: D018076:DNA, Complementary; D005700:Galactosyltransferases; C063053:xylosylprotein 4-beta-galactosyltransferase