Antithrombin deficiency caused by SERPINC1 gene mutations predispose to venous thrombotic events
10.3760/cma.j.cn114452-20220301-00110
- VernacularTitle:SERPINC1基因缺陷导致的AT缺陷症患者易发生静脉血栓事件
- Author:
Haixiao XIE
1
;
Yuan CHEN
;
Qiyu XU
;
Xingxing ZHOU
;
Kaiqi JIA
;
Manlin ZENG
;
Lihong YANG
;
Mingshan WANG
Author Information
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
- Keywords:
Antithrombin deficiency;
SERPINC1 gene;
Genetic mutation;
Thrombosis
- From:
Chinese Journal of Laboratory Medicine
2023;46(2):203-208
- CountryChina
- Language:Chinese
-
Abstract:
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 type Ⅰ AT deficiency, and the AT: Ag of the other 5 patients were normal, presented type Ⅱ AT 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.
