Gilbert综合征和Crigler-Najjar综合征相关尿苷二磷酸葡糖醛酸转移酶A1基因突变位点特征分析  

Analysis of mutation site characteristics of Gilbert syndrome and Crigler--Najjar syndrome in relation to uridine diphosphate glucuronosyltransferase A1 gene

作　　者：梁晨 罗磊 白洁 白丽 卞丹丹 任艳 刘霜 陈煜 段钟平 郑素军 Liang Chen;Luo Lei;Bai Jie;Bai Li;Bian Dandan;Ren Yan;Liu Shuang;Chen Yu;Duan Zhongping;Zheng Sujun(Difficult&Complicated Liver Diseases and Artificial Liver Center,Beijing Youan Hospital,Capital Medical University,Beijing 100069,China;Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research,Beijing 100069,China;Department of Infectious Diseases,Electric Power Teaching Hospital,Capital Medical University,Beijing 100073,China)

机构地区：[1]首都医科大学附属北京佑安医院疑难肝病及人工肝中心,北京100069 [2]肝衰竭与人工肝治疗研究北京市重点实验室,北京100069 [3]首都医科大学电力教学医院感染性疾病科,北京100073

出　　处：《中华肝脏病杂志》2020年第5期428-433,共6页Chinese Journal of Hepatology

基　　金：北京市医院管理局消化内科学科协同发展中心项目(XXZ0503);科技创新服务能力建设-高精尖学科建设项目(市级)(11920703);国家科技重大专项"艾滋病和病毒性肝炎等重大传染病防治"(2012ZX10002004-006、2017ZX10203201-005、2017ZX10201201-001-001、2017ZX10201201-002-002、2017ZX10201201-004-002、2017ZX10202203-006-001、2017ZX10302201-004-002);国家重点研发计划资助(2017YFA0103000);北京市医院管理局"登峰"人才培养计划基金资助项目(DFL20151601);北京市医院管理局临床医学发展专项经费(ZYLX201806)。

摘　　要：目的探讨Gilbert综合征(GS)和Crigler-Najjar综合征(CNS)相关尿苷二磷酸葡糖醛酸转移酶A1(UGT1A1)基因的突变特征及与临床的相关性。方法通过检索PubMed和人类基因突变数据库归纳UGT1A1基因突变位点的特征并分析其临床相关性。结果截至2018年11月16日,共发现UGT1A1基因163个突变位点,上述位点存在以下规律:(1)GS或CNS表型相关的UGT1A1的不同外显子发生的基因突变个数,均与外显子长度呈正相关;(2)无义点突变主要发生在CNS I型;(3)GS、CNS II型的复合杂合突变位点的组合和分布存在一定规律,其中GS的4种复合杂合组成中,均有-3279T>G突变;(4)亚洲地区报道的UGT1A1基因突变位点在c.211-c.558有明显的聚集性。结论UGT1A1基因突变位点不同、报道地区不同及人群不同,其突变特征及临床相关性也不同。本研究对GS和CNS的基础研究和临床诊疗有参考价值。Objective To investigate the mutation characteristics and clinical relevance of Gilbert syndrome(GS)and Crigler-Najjar syndrome(CNS)in relation to uridine diphosphate glucuronosyltransferase A1(UGT1A1)gene.Methods The characteristics of UGT1A1 gene mutation and their clinical relevance were analyzed by searching PubMed and Human Gene Mutation Databases.Results A total of 163 mutation sites were found in the UGT1A1 gene since November 16,2018.The following patterns existed at the above sites:(1)the numbers of gene mutations occurring between different exons of UGT1A1 was related to GS or CNS phenotypes,and were positively correlated with the length of the exon;(2)nonsense point mutations was mainly occurred in type I of CNS;(3)GS,Crigler-Najjar syndrome type II compound heterozygous mutation sites had a certain combination and distribution,among which-3279t>G mutation was found in all four GS complex heterozygous compositions;(4)UGT1A1 gene mutation sites reported in Asia had marked aggregation in c.211-c.558.Conclusion UGT1A1 gene mutation characteristics and clinical relevance varies with different mutation sites,reporting areas and populations.This study has reference value for basic research and clinical diagnosis and treatment of GS and CNS.

关 键 词：GILBERT综合征 Crigler-Najjar综合征 基因突变位点 

分 类 号：R575[医药卫生—消化系统]