SERPINC1基因缺陷导致的AT缺陷症患者易发生静脉血栓事件  

Antithrombin deficiency caused by SERPINC1 gene mutations predispose to venous thrombotic events

作　　者：谢海啸[1] 陈元 徐琦煜[1] 周星星[1] 贾恺琦 曾蔓霖 杨丽红[1] 王明山[1] Xie Haixiao;Chen Yuan;Xu Qiyu;Zhou Xingxing;Jia Kaiqi;Zeng Manlin;Yang Lihong;Wang Mingshan(Department of Clinical Laboratory,Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China)

机构地区：[1]温州医科大学附属第一医院医学检验中心,浙江省检验诊断及转化研究重点实验室,温州325015

出　　处：《中华检验医学杂志》2023年第2期203-208,共6页Chinese Journal of Laboratory Medicine

基　　金：温州市科技局项目(Y20220126);浙江省检验诊断及转化研究重点实验室(2022E10022)。

摘　　要：目的分析12例抗凝血酶(AT)缺陷症患者的基因突变,探讨SERPINC1基因突变与静脉血栓事件的关系。方法本文研究类型为观察性研究-描述性研究:病例系列。收集2014年4月至2021年4月温州医科大学附属第一医院12例AT缺陷患者临床资料,在患者治疗前,采集血标本。采用发色底物法检测血浆AT活性(AT:A),免疫比浊法检测AT抗原(AT:Ag)含量。采用PCR直接测序法分析先证者SERPINC1基因7个外显子及其侧翼序列,对发现的疑似突变用反向测序予以验证。分析SERPINC1基因突变与患者静脉血栓栓塞症(VTE)的相关性,统计占比。结果12例患者的AT:A在30%~66%,均明显下降,7例患者的AT:Ag同步降低,表现为Ⅰ型AT缺陷,5例患者AT:Ag在参考范围,表现为Ⅱ型AT缺陷。共发现12种SERPINC1基因突变,其中6种杂合突变c.456_458delCTT(p.phe121del)、c.318_319insT(p.Asn75stop)、c.922G>T(p.Gly276Cys)、c.938T>C(p.Met281Thr)、c.1346T>A(p.Leu417Gln)和c.851T>C(p.Met252Thr)为首次发现的突变位点。12例患者均有静脉血栓形成表现,其中3例患者包括2例复合杂合突变患者和1例单杂合突变患者,在没有明显诱因下,青壮年时期即发生深静脉血栓(DVT);其他9例患者合并有其他易栓危险因素,包括高龄、高血压、吸烟、妊娠和制动。结论SERPINC1基因缺陷导致的AT缺陷症患者易发生静脉血栓事件,尤其当同时存在其他易栓因素时。Objective To analyze 12 antithrombins(AT)gene mutations that cause AT deficiency and discuss the relationship between the SERPINC1 gene.mutations and venous thrombotic events.Methods This study belongs to case series of observational studies.Collected the clinical data of 12 AT deficiency cases in the First Affiliated Hospital of Wenzhou Medical University from April 2014 to April 2021 and collected the blood samples before treatment.The AT activity(AT:A)and AT antigen(AT:Ag)was detected by chromogenic substrate and immunoturbidimetry,respectively.The 7 exons and flanking sequences of the SERPINC1 gene were sequenced directly by PCR,the suspected mutations were validated by reverse sequencing.Analyzed the correlation between the SERPINC1 gene.mutations and venous thrombotic events and figured out the proportion.Results The AT:A of the 12 patients all decreased significantly,ranging from 30%to 66%,and the AT:Ag of the 7 patients decreased accordingly,showing typeⅠAT deficiency,and the AT:Ag of the other 5 patients were normal,presented typeⅡAT deficiency.12 mutations were found including 6 heterozygous mutations which were discovered for the first time:c.456_458delCTT(p.phe121del),c.318_319insT(p.Asn75stop),c.922G>T(p.Gly276Cys),c.938T>C(p.Met281Thr),c.1346T>A(p.Leu417Gln)and c.851T>C(p.Met252Thr).All 12 patients had venous thrombosis,and 3 cases including 2 compound heterozygotes and 1 single heterozygote all suffered from deep venous thrombosis(DVT)when they were younger without obvious triggers.The other 9 patients all combined with the other thrombotic factors including old age,hypertensive,smoking,pregnancy,and prolonged immobilization.Conclusion Patients with AT deficiency caused by SERPINC1 gene defects are prone to venous thrombosis,especially combined with other thrombotic factors.

关 键 词：抗凝血酶缺陷症 SERPINC1基因 基因突变 血栓形成 

分 类 号：R596[医药卫生—内科学] R543.6[医药卫生—临床医学]