Galactosyltransferase I is a gene responsible for progeroid variant of Ehlers-Danlos syndrome: molecular cloning and identification of mutations

• Published in: BBA - General Subjects Vol. 1573; no. 3; pp. 377 - 381
• Main Authors: Furukawa, Koichi, Okajima, Tetsuya
• Format: Book Review Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 19.12.2002; Elsevier BV
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Caenorhabditis elegans; Cloning, Molecular; DNA, Complementary; Ehlers-Danlos Syndrome; Ehlers-Danlos Syndrome - enzymology; Ehlers-Danlos Syndrome - genetics; Ehlers-Danlos Syndrome - physiopathology; Galactosyltransferase I; Galactosyltransferases; Galactosyltransferases - genetics; Humans; Molecular Sequence Data; Mutation; Syndrome; Galactosyltransferase I; Ehlers-Danlos syndrome; Mutation
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/S0304-4165(02)00406-3

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-β- d-xylopyranoside, and also restored glycosaminoglycan (GAG) synthesis to galactosyltransferase I-deficient CHO mutant pgsB-761 cells. The enzyme product contained β-1,4-linked galactosyl residues, indicating that the enzyme is galactosyltransferase I (UDP- d-galactose: d-xylose β-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).