遗传性易栓症筛查及相关基因检测分析

doi:10.3785/j.issn.1008-9292.2018.12.07

浙江大学学报（医学版）

2018, Vol. 47

Issue (6): 606-611 DOI: 10.3785/j.issn.1008-9292.2018.12.07

专题报道

遗传性易栓症筛查及相关基因检测分析

尹黎¹(

),李歌²,沈健³,刘震杰^1,*(

)

1. 浙江大学医学院附属第二医院血管外科, 浙江杭州 310009
2. 浙江大学医学院附属邵逸夫医院病理科, 浙江杭州 310006
3. 浙江大学医学院附属第二医院心血管研究所, 浙江杭州 310009

Screening for inherited thrombophilia and genome sequencing

YIN Li¹(

),LI Ge²,SHEN Jian³,LIU Zhenjie^1,*(

)

1. Department of Vascular Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
2. Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
3. Institute of Cardiovascular Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China

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摘要：

目的: 检测和分析遗传性易栓症的相关基因及其突变位点，为中国人群遗传性易栓症患者的基因突变特点积累资料。方法: 对2015年6月至2017年12月在浙江大学医学院附属第二医院就诊的遗传性易栓症疑似患者25例进行血清蛋白C、蛋白S，抗凝因子相关基因蛋白C（基因名PROC）、蛋白S（基因名PROS1）和抗凝血酶Ⅲ（基因名SERPINC1），凝血因子相关基因凝血因子Ⅴ（基因名F5）、凝血因子Ⅱ（基因名F2）、凝血因子Ⅷ（基因名F8）、高型半胱氨酸血症相关因子（CBS、MTHFR）第二代测序分析。利用千人基因组数据库、ESP6500数据库、Genoma数据库、HGMD突变数据库比对突变位点，根据SIFT、Polyphen、MutationTaster、CADD数据库预测突变位点的致病性。结果: 25例患者中，发现抗凝因子相关基因PROC突变患者8例，PROS1突变患者2例，SERPINC1突变患者3例；凝血相关基因F5突变1例，F2突变1例，F8突变1例，CBS突变2例，MTHFR突变1例。结论: 应用第二代基因测序分析有助于诊断遗传性易栓症相关静脉血栓，指导精准治疗。

关键词： 静脉血栓形成/遗传学; 血栓形成倾向/遗传学; 血液凝固; 抗凝血酶类; 基因; 突变

Abstract:

Objective: To screening coagulation and anticoagulation genes and mutations in Chinese patients with venous thromboembolism suspected of inhered thrombophilia. Methods: Patients with venous thromboembolism caused by inherited thrombophilia were collected from the second Affiliated Hospital, Zhejiang University School of Medicine during June 2015 and December 2017. Gene sequencing was conducted to screen the anticoagulant-related genes PROC, PROS1, SERPINC1 and coagulation-related genes F5, F2, F8, CBS, MTHFR. The thousands of human genome database, ESP6500 database, Genoma database, HGMD mutation database were used to compare the mutation sites, and the pathogenic mutation sites were predicted according to SIFT, Polyphen, MutationTaster and CADD databases. Results: Among 25 patients screened, eight patients with PROC mutations, two patients with PROS1 mutations, three patients with SERPINC1 mutations; one patient with F5 mutation, one patient with F2 mutation, one patient with F8 mutation, two patient with CBS mutations, and one patient with MTHFR mutation. Conclusion: The second generation gene sequencing helps to diagnose inherited thrombophilia and guide the decision of anticoagulation duration.

Key words: Venous thrombosis/genetics Thrombophilia/genetics Blood coagulation Antithrombins Genes Mutation

收稿日期: 2018-08-14 出版日期: 2019-03-15

R446

基金资助: 国家自然科学基金(81300236, 81670433)

通讯作者: 刘震杰 E-mail: yinli18c@zju.edu.cn;lawson4001@zju.edu.cn

作者简介: 尹黎(1990-), 女, 博士, 住院医师, 主要从事血管外科基础及临床研究; E-mail:yinli18c@zju.edu.cn; https://orcid.org/0000-0003-2008-9738

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引用本文:

尹黎,李歌,沈健,刘震杰. 遗传性易栓症筛查及相关基因检测分析[J]. 浙江大学学报（医学版）, 2018, 47(6): 606-611.

YIN Li,LI Ge,SHEN Jian,LIU Zhenjie. Screening for inherited thrombophilia and genome sequencing. J Zhejiang Univ (Med Sci), 2018, 47(6): 606-611.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2018.12.07 或 http://www.zjujournals.com/med/CN/Y2018/V47/I6/606

图 1 疑似遗传性易栓症患者的筛查流程

表 1 抗凝因子基因突变患者的突变位点及类型

图 2 一例蛋白C缺乏症患者的遗传系谱及基因突变位点

表 2 凝血因子基因突变患者的突变位点及类型

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