Yamamoto K, Sato H, Fujiyama Y, Doida Y, Bamba T
Second Department of Internal Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-21, Japan.
Biochim Biophys Acta. 1998 Apr 28;1406(3):267-73. doi: 10.1016/s0925-4439(98)00013-1.
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.
在我们对胆红素UDP糖基转移酶（UGT1A1）基因的突变分析中，我们遇到了6例II型克里格勒-纳贾尔综合征患者，他们是G71R和Y486D的双重纯合子，1例吉尔伯特综合征患者是G71R的单一纯合子，还有6例吉尔伯特综合征患者是G71R的单一杂合子。为了阐明每个突变在这两种综合征发生中的作用，我们构建了4种突变表达模型。G71R单一纯合模型的相对UGT1A1活性为正常水平的32.2±1.6%，Y486D单一纯合模型的相对UGT1A1活性为7.6±0.5%，G71R和Y486D双重纯合模型的相对UGT1A1活性为6.2±1.6%，G71R杂合模型的相对UGT1A1活性为60.2±3.5%。G71R单一纯合模型和双重纯合模型活性的降低程度分别处于可被诊断为吉尔伯特综合征和II型克里格勒-纳贾尔综合征的适当水平。G71R单一杂合模型的活性略高，不太可能发展为吉尔伯特综合征的表型，这表明吉尔伯特综合征的病因中存在其他因素。
