全外显子测序检测一个遗传性易栓症家系的致病基因

Identification of causative gene in a Chinese family with inherited thrombophilia by whole exome sequencing

目的对一例遗传性易栓症家系进行基因分析。方法对一个遗传性易栓症家系成员进行凝血因子、凝血功能检测,对2名患病的家系成员进行全外显子测序确定候选基因,对所有家系成员及正常对照组进行候选突变基因的Sanger测序验证。结果全外显子测序提示这个家系存在凝血因子Ⅱ基因的T165M突变。结论该易栓症家系的发病原因为凝血因子Ⅱ基因的第六外显子c.C494T(p.T165M)突变,全基因组外显子测序能解决传统定位克隆技术常常面临该病家系患者太少、病例散发、基因位点的异质性、外显不全及候选基因太多等难题,为该病产前诊断提供了新的途径。

Objective：To investigate gene mutation in a inherited thrombophilia family. Methods：The levels of blood coagulation factor and coagulation study was measured,Whole exome sequencing was conducted use DNA samples of two affected members of this family.Candidate mutation was confirmed by Sanger sequencing. Results：Whole exome sequencing revealed an exonic missense mutation c.C494T：p.T165 Min coagulation factor Ⅱ gene. Conclusion：We have identified and confirmed that the T165 M mutation in F2 may have caused thrombophilia in a Chinese family,The technology for the whole genome exome sequencing can solve many problems of the traditional positional cloning,such as too few of the patients of the family members of this disease,sporadic cases,heterogeneity of the genetic locus,incomplete exon,too many candidate genes and so on,to provide new solutions of the prenatal diagnosis of this disease.