title: Contribution of two missense mutations (G71R and Y486D) of the bilirubin UDP glycosyltransferase (UGT1A1) gene to phenotypes of Gilbert's syndrome and Crigler-Najjar syndrome type II.
abstract: In our mutation analyses of bilirubin UDP glycosyltransferase (UGT1A1) gene, we encountered six patients with Crigler-Najjar syndrome type II who were double homozygotes for G71R and Y486D, a patient with Gilbert's syndrome who was a single homozygote for G71R and six patients with Gilbert's syndrome who were single heterozygote for G71R. To clarify the role of each mutation in the occurrence of the two syndromes, we made four mutant expression models. Relative UGT1A1 activity of a single homozygous model of G71R was 32.2+/-1.6% of normal, that of a single homozygous model of Y486D was 7.6+/-0.5%, that of a double homozygous model of G71R and Y486D was 6.2+/-1.6% and that of a heterozygous model of G71R was 60.2+/-3.5%. The decreased activities of the single homozygous model of G71R and the double homozygous model were at an appropriate level to be diagnosed as Gilbert's syndrome and CN-II, respectively. The activity of a single heterozygous model of G71R was somewhat high to develop to the phenotype of Gilbert's syndrome, suggesting the presence of additional factors for the etiology of Gilbert's syndrome.
authors.affiliation: Second Department of Internal Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-21, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Doida
authors.forename: T
authors.initials: T
authors.lastname: Bamba
mesh_terms: D000818:Animals; D001120:Arginine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D015153:Blotting, Western; D019556:COS Cells; D003414:Crigler-Najjar Syndrome / Q000145:classification / Q000201:enzymology* / Q000235:genetics*; D004789:Enzyme Activation / Q000235:genetics; D005878:Gilbert Disease / Q000201:enzymology* / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D005998:Glycine / Q000235:genetics; D006720:Homozygote; D006801:Humans; D020125:Mutation, Missense; D010641:Phenotype; D014162:Transfection; D014443:Tyrosine / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D001120:Arginine; D001224:Aspartic Acid; D014453:Glucuronosyltransferase; D005998:Glycine; D014443:Tyrosine; D000099148:UGT1A1 Enzyme