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
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
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DOI：
10.1016/s0925-4439(98)00013-1
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发表时间：
1998-04-28
影响因子：
6.2
通讯作者：
Bamba, T
中科院分区：
文献类型：
--
作者：
Yamamoto, K;Sato, H;Bamba, T
在我们的胆红素UDP糖基转移酶（UGT 1A 1）基因突变分析中，我们遇到了6例Crigler-Najjar综合征II型患者，他们是G71 R和Y 486 D的双纯合子，1例吉尔伯特综合征患者是G71 R的单纯合子，6例吉尔伯特综合征患者是G71 R的单杂合子。为了阐明每个突变在两种综合征发生中的作用，我们制作了四个突变表达模型。G71 R单纯合子模型的相对UGT 1A 1活性为正常值的32.2 +/- 1.6%，Y 486 D单纯合子模型的相对UGT 1A 1活性为7.6 +/-0.5%，G71 R和Y 486 D双纯合子模型的相对UGT 1A 1活性为6.2 +/- 1.6%，G71 R杂合子模型的相对UGT 1A 1活性为60.2 +/-3.5%。G71 R单纯合模型和双纯合模型的活性降低分别处于诊断为吉尔伯特综合征和CN-II的适当水平。单个G71 R杂合子模型的活性略高，发展为吉尔伯特综合征的表型，表明吉尔伯特综合征的病因存在其他因素。(C)1998 Elsevier Science B. V.保留所有权利。
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. (C) 1998 Elsevier Science B.V. All rights reserved.