一个Gilbert综合征家系的基因诊断和遗传分析  

Gene diagnosis and genetic analysis of a Gilbert's syndrome pedigree

作　　者：曹雅楠[1,2] 王学锋[1] 丁秋兰[1] 许冠群[1] 张利伟[1] 戴菁[1] 陆晔玲[1] 奚晓东[2] 王鸿利[2] 

机构地区：[1]上海交通大学医学院附属瑞金医院临床检验科,上海200025 [2]上海交通大学医学院附属瑞金医院上海血液学研究所,上海200025

出　　处：《诊断学理论与实践》2012年第4期344-348,共5页Journal of Diagnostics Concepts & Practice

摘　　要：目的:对1例Gilbert综合征患者进行基因诊断,并对其家系成员进行相关基因UGT1A1检测及遗传学分析。方法:排除其他相关疾病,结合低热卡试验结果和病史特点确诊1例Gilbert综合征患者。抽取患者及其家系成员的外周静脉血,提取基因组DNA,用聚合酶链反应(PCR)方法扩增相关基因UGT1A1,扩增产物直接测序,比对鉴定。结果:Gilbert综合征先证者的血清总胆红素升高,并以间接胆红素升高为主。低热卡试验中,先证者限制热量摄入后血清胆红素较限制热量前升高2倍,有诊断意义。基因检测发现,先证者及其胞姐同为UGT1A1基因启动子区域TA盒TA插入的A(TA)7TAA型,其父母UGT1A1基因的TA盒区域均为A(TA)6/(TA)7TAA杂合型。结论 :UGT1A1基因启动子中的TA插入影响了先证者的胆红素代谢水平,此基因异常是导致Gilbert综合征家系发病的原因,且该突变的遗传方式符合常染色体隐性遗传。Objective To diagnosis a Gilbert＇s syndrome patient on the basis of gene, testing her first degree relatives for the relative gene and making an analysis of heredity. Methods By ruling out other related diseases and in accordance with the result of low calorie diet test and characteristic history, a case of Gilbert＇s syndrome was diagnosed. Blood samples were collected from the patient and her first degree relatives and the genomic DNA was extracted. Amplified the relative gene UGT1A1 by polymerase chain reaction （PCR） and mutations were identified by direct sequencing. Results The patient＇s unconjugated bilirubin （UCB） is higher than normal and lead to a high total bilirubin. The low calorie diet test showed that after taking the low calorie diet , the patient＇s UCB was two times higher than before. The patient and her sister had a TA insertion in TATA box of the promoter region as A （TA）7TAA . Their parents are both heterozygote individuals with A （TA）6/（TA）TTAA. Conclusions The TA insertion in the promoter region of the UGT1A1 gene affects the bilirubin metabolism of the patient. The A（TA）7TAA is essential for the pathogenesis of Gilbert＇s syndrome and is inherited in an autosomal recessive manner.

关 键 词：GILBERT综合征 尿苷二磷酸葡萄糖醛酸转移酶 突变 家系 

分 类 号：R446[医药卫生—诊断学]