CONTRIBUTION OF 2 MISSENSE MUTATIONS (G71R AND Y486D) OF THE BILIRUBIN UDP GLYCOSYLTRANSFERASE (UGT1A1) GENE TO PHENOTYPES OF GILBERTS-SYNDROME AND CRIGLER-NAJJAR-SYNDROME TYPE-II

In our mutation analyses of bilirubin UDP glycosyltransferase (UGT1A1) gene, we encountered six patients with Crigler-Najjar syndrome type I I who were double homozygotes for G71R and Y486D, a patient with Gilbe rt's syndrome who was a single homozygote for G71R and six patients wi th Gilbert's syndrome who were single heterozygote for G71R. To clarif y the role of each mutation in the occurrence of the two syndromes, we made four mutant expression models. Relative UGT1A1 activity of a sin gle homozygous model of G71R was 32.2 +/- 1.6% of normal, that of a si ngle homozygous model of Y486D was 7.6 +/- 0.5%, that of a double homo zygous model of G71R and Y486D was 6.2 +/- 1.6% and that of a heterozy gous model of G71R was 60.2 +/- 3.5%. The decreased activities of the single homozygous model of G71R and the double homozygous model were a t an appropriate level to be diagnosed as Gilbert's syndrome and CN-II , respectively. The activity of a single heterozygous model of G71R wa s somewhat high to develop to the phenotype of Gilbert's syndrome, sug gesting the presence of additional factors for the etiology of Gilbert 's syndrome. (C) 1998 Elsevier Science B.V. All rights reserved.