Wen Si-Yuan, Chen Fei-Fei, Chen Ji-De, Tao Pan, Meng Chi, Huang Jing, Kang Xin, Chen Wei, Zhou Chang-Qing
Department of Neurology, Bishan Hospital of Chongqing Medical University, Chongqing, China.
Department of Clinical Laboratory, Bishan Hospital of Chongqing Medical University, Chongqing, China.
Res Pract Thromb Haemost. 2025 Jul 29;9(5):102987. doi: 10.1016/j.rpth.2025.102987. eCollection 2025 Jul.
Inherited thrombophilia (IT) is a genetically determined predisposition to thromboembolic events. Beyond the well-known G20210A mutation, there has been limited research on other prothrombin mutations in the Chinese population.
This study aimed to identify and characterize a novel prothrombin mutation in a Han Chinese family with IT.
Clinical information was collected from the proband and his related family members. Coagulation tests, including protein S, plasminogen, protein C, and antithrombin Ⅲ activities, were conducted. Whole-genome sequencing was conducted on the proband and his mother to identify the causative mutation, and suspected mutations were verified in other family members using whole-exon sequencing. Thrombin generation assay was performed to evaluate hypercoagulable states.
Among the 53 family members, 11 individuals had a history of venous thromboembolism (VTE). Genetic analysis of 9 family members identified a novel heterozygous prothrombin mutation, p.Ile441Met (c.1323A>G), in 6 individuals with VTE history. These mutation carriers exhibited various forms of VTE, predominantly pulmonary embolism and lower-limb deep vein thrombosis. Routine coagulation tests showed no significant abnormalities in prothrombin time and activated partial thromboplastin time, while 5 carriers exhibited decreased protein S activity. Thrombin generation assay revealed a hypercoagulable state, characterized by shortened lag time, increased thrombin peak, and elevated endogenous thrombin potential.
The Ile441Met mutation is a novel prothrombin mutation associated with IT in the Han Chinese population, which induces a hypercoagulable state, leading to various forms of VTE. Further studies are needed to validate these findings and investigate the underlying pathogenic mechanisms.
遗传性血栓形成倾向（IT）是一种由基因决定的易发生血栓栓塞事件的倾向。除了众所周知的G20210A突变外，在中国人群中，对其他凝血酶原突变的研究有限。
本研究旨在鉴定并表征一个患有IT的汉族家庭中的一种新型凝血酶原突变。
收集先证者及其相关家庭成员的临床信息。进行了包括蛋白S、纤溶酶原、蛋白C和抗凝血酶Ⅲ活性在内的凝血试验。对先证者及其母亲进行全基因组测序以鉴定致病突变，并使用全外显子测序在其他家庭成员中验证疑似突变。进行凝血酶生成试验以评估高凝状态。
在53名家庭成员中，11人有静脉血栓栓塞（VTE）病史。对9名家庭成员的基因分析在6名有VTE病史的个体中鉴定出一种新型杂合凝血酶原突变，p.Ile441Met（c.1323A>G）。这些突变携带者表现出各种形式的VTE，主要是肺栓塞和下肢深静脉血栓形成。常规凝血试验显示凝血酶原时间和活化部分凝血活酶时间无明显异常，而5名携带者的蛋白S活性降低。凝血酶生成试验显示高凝状态，其特征为滞后时间缩短、凝血酶峰值增加和内源性凝血酶潜力升高。
Ile441Met突变是中国汉族人群中一种与IT相关的新型凝血酶原突变，它诱导高凝状态，导致各种形式的VTE。需要进一步研究来验证这些发现并探究潜在的致病机制。
