家系分析显示Gilbert综合征是由UGT1A1基因多态性-第三军医大学学报.docVIP

8例Gilbert综合征家系UGT1A1变异谱调查及分析 李露锋，邓国宏，谭文婷，郭鑫武,但芸婕，李艳华，唐 怡，毛 青 （400038 重庆，第三军医大学西南医院全军感染病研究所） ［摘要］ 目的 研究Gilbert综合征与UGT1A1变异的关系。方法 选取8例Gilbert综合征家系成员外周静脉血提取基因组DNA，采用聚合酶链反应（PCR）扩增UGT1A1基因上游的启动子TATA盒及第1～5外显子序列，PCR产物测序后行遗传作图分析；并对先症者进行1年以上的随访观察。结果 在6例完整的核心家系中，先症者双亲的发病率仅为25%（小于50%）。4例先症者各有1名兄妹，其中1例先症者的同卵双胎也发病，而其余3例先症者只有1例的弟弟发病。1例家系第2代4名女性中只有1人发病。共检测到3个错义突变位点（c.211GA，p.G71R，rs4148323；c.686CA，p.P229Q，rc.1091CT，p.P364L，r和1个位于启动子区TATA盒的2个额外碱基TA插入变异（c.-40_-39insTA）。所有15例患者中（包括8例先症者和7例家系成员），12例携带UGT1A1的纯合变异或2个无连锁（1个来自父亲，1个来自母亲）的杂合变异（0.80），3例患者仅携带单个UGT1A1基因的杂合变异；而携带单个杂合变异的14例家系成员中仅有1例表现为Gilbert综合征，其余13例胆红素水平均正常。结论 Gilbert综合征与UGT1A1的变异相关，并呈现出叠加效应，携带纯合变异或2个不连锁杂合变异者容易表现为Gilber综合征，而大多数携带单个杂合变异者则表现为正常。 ［关键词］ Gilbert综合征；遗传模式；家系分析；UGT1A1；变异；多态性 ［中图法分类号］ R575.5；Q39；Q31 [文献标志码] A Investigation and analyses of UGT1A1 variant spectrum for eight Gilbert syndrome families Li Lufeng, Deng Guohong, Tan Wenting, Guoxinwu, Dan Yunjie, Li Yanhua, Tang Yi, Mao Qing (Institute of Infection Diseases, Southwest Hospital, Third Military University, Chongqing, 400038, China) ［Abstract］ Objective To study correlation of Gilbert syndrome (GS) and UGT1A1 variations. Methods The genome DNA was extracted from the peripheral blood of eight probands and their family members. The promoter and coding regions of UGT1A1 were amplified by polymerase chain reaction (PCR). We sequenced the amplified DNA fragments and then made family pedigree analysis; bilirubin levels of all probands were followed-up investigated for at least one year. Results Incidence of parents of probands is less than 50% (25%) in 6 complete nuclear families. The twin brother of a proband is also a Gilbert syndrome patient. Only one brother of the proband is affected in other 3 families in which the probands have a brother or sister. Only a sister was detected with unconjugated hyperbilirubinemia in four sisters of the second generations. Three missensevariants in coding regions (c.211GA, p.G71R in