对一个中国汉族G ilbert综合征遗传家系致病基因突变位点进行鉴定,以期了解该病的分子遗传学基础。首先提取先证者基因组DNA,PCR扩增尿苷二磷酸葡萄糖醛酸转移酶UGT1A1基因的5个外显子,以琼脂糖电泳鉴定PCR产物,纯化后直接测序鉴定。基因扫描显示,与血清胆红素水平密切相关的UGT1A1基因在第1和第5外显子存在纯合突变,而UGT1A1基因启动子区域和内含子/外显子剪接边界位点序列未检测到突变。进一步对其他家系成员该基因的相应位点进行突变检测,结果显示他们在第1和第5外显子也存在杂合突变,其中还有两个成员在启动子区域检测到(TA)插入突变。对家系成员未抗凝新鲜血液进行生化检测证实了基因突变分析的结果。综合以上结果发现该家系3种突变并存,致病因素为第1和/或第5外显子突变,为显性遗传,两种突变位点纯合导致先证者出现严重胆红素代谢功能障碍。该家系因此成为G ilbert综合征突变位点及其致病机理研究的一个典型临床病例。 To identify the causative gene mutation sites of Gilbert syndrome in a Han Chinese in order to understand the molecular genetic basis of the disease. First, the proband’s genomic DNA was extracted and five exons of UGT1A1 gene of uridine diphosphate glucuronosyltransferase were amplified by PCR. The PCR products were identified by agarose gel electrophoresis and directly sequenced and identified. Gene scan showed that UGT1A1 gene closely related to serum bilirubin had homozygous mutation in exon 1 and exon 5 while the UGT1A1 gene promoter region and intron / exon splicing border site sequence were not detected To mutation. Mutations were detected in the corresponding loci of other members of the pedigree. The results showed that there were also heterozygous mutations in exon 1 and exon 5, and two of them also detected a (TA) insertion mutation in the promoter region . Biochemical tests on members of the family who did not anticoagulant fresh blood confirmed the results of the gene mutation analysis. Based on the above results, it was found that there were three mutations in this pedigree. The causal factors were the first and / or the fifth exon mutations, which were dominant inheritance. Homozygous loci of the two mutations resulted in severe bilirubin metabolism in probands obstacle. The pedigree therefore became a typical clinical case of Gilbert syndrome mutation site and its pathogenesis.