35个肝豆状核变性家系ATP7B基因的突变分析  

Mutation analysis of 35 Wiison＇s disease pedigrees

作　　者：宗亚楠 孔祥东[1] 

机构地区：[1]郑州大学第一附属医院产前诊断中心,450052

出　　处：《中华医学遗传学杂志》2016年第1期30-33,共4页Chinese Journal of Medical Genetics

基　　金：河南省卫生厅科技攻关项目（201303015）

摘　　要：目的了解肝豆状核变性家系先证者ATP7B基因突变的特点，并探讨其产前及症状前诊断的可行性。方法对先证者及其父母应用Sanger测序检测ATP7B基因的全部21个外显子，对7个家系中的高风险成员进行症状前诊断，对其中4个家系于孕11～13周抽取胎盘绒毛组织进行产前基因诊断，并通过连锁分析验证测序结果。结果在35例先证者中，共检测出65个ATP7B基因突变（92．9％），其中31例先证者检出2个等位突变，3例先证者仅检出1个ATP7B基因等位突变，1例先证者未发现突变。共发现24种ATP7B基因突变，13种单核苷酸多态性，其中包括7种新突变．c．3871G〉A（p．A1291T）、c．2593—2594insGTCA、c．2790—2792delCAT、c．3661—3663delGGG、c．3700delG、C．4094—4097delCTGT、IVS6＋1G〉A。最常见的突变为C．2333G〉T（P．R778L）（45．7％）、c．2621C〉T（P．A874V）（7．1％）以及C．2975C〉T（p．P992L）（7．1％）。共诊断出2例症状前患者；产前诊断的胎儿中3例为正常基因型，另1例为杂合携带者，出生后随访胎儿均正常。结论本研究中ATP7B基因最常见的突变为R778L，共发现7种ATP7B基因的新突变。联合应用Sanger测序和连锁分析可对肝豆状核变性家系进行快速准确的产前及症状前诊断。Objective To analyze the features of genetic mutations underlying Wilson＇s disease and provide prenatal and presymptomatic diagnosis. Methods For 35 pedigrees affected with the disease, the exons and exon-intron boundaries of the ATPTB gene were amplified with polymerase chain reaction and subjected to Sanger sequencing. After the genotypes of parents of the probands were determined, prenatal diagnosis were performed through chorionic villus sampling. Results The overall rate for mutation detection was 92. 9%. A total of 24 distinct mutations were detected, which included 7 novel mutations, i. e. , c. 3871G〉A（p. A1291T）, c. 2593_ 2594insGTCA, c. 2790_2792delCAT, c. 3661_3663delGGG, c. 3700delG, c. 4094_4097delCTGT, and IVS6＋IG〉A. Three mutations, including R778L （c. 2333G〉T） （45.7%）, A874V （c. 2621C〉T） （7. l~//00） and P992L （c. 2975C〉T） （7. 1%）, were relatively common. Two presymptomatic patients were detected through familial screening, for whom treatment was initiated. Prenatal genetic diagnosis has verified three healthy fetuses and one carrier. Conclusion In this study the most popular mutation of ATPTB gene is R778L and 7 novel mutations have been identified in this gene. For pedigrees of Wilson＇s disease, genetic counseling in addition with prenatal and presymptomatic diagnosis should be provided through Sanger sequencing and haplotype analysis.

关 键 词：肝豆状核变性 ATP7B基因 突变分析 产前诊断 症状前基因诊断 

分 类 号：R742.4[医药卫生—神经病学与精神病学]