Clinical characteristics, genes identification and follow-up study of a patient with central venous thrombosis from a protein S deficiency pedigree
Clinical characteristics, genes identification and follow-up study of a patient with central venous thrombosis from a protein S deficiency pedigree
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1例蛋白S缺乏家系中心静脉血栓患者的临床特征、基因鉴定及随访研究
DOI：
10.26355/eurrev_202101_24402
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发表时间：
2021-01-01
影响因子：
3.3
通讯作者：
Ma, L.
中科院分区：
文献类型：
--
作者：
Wang, T.;Zhao, X-J;Ma, L.
目的：探讨PROS1基因突变所致CVT的临床及预后特点，为利伐沙班等新型口服抗凝药物治疗高危血栓性CVT提供临床经验。患者和方法：描述CVT患者的临床症状，并进行脑成像和凝血检查以确认CVT的诊断。招募患者家属接受凝血检查和下肢血管超声检查。通过家系遗传分析，确定了PS缺乏症的致病基因。我们对该患者进行了24个月的随访，评估CVT的临床结果、实验室结果和影像学表现。结果：患者表现出典型的CVT症状，包括头痛和癫痫。脑CT示双侧额叶及左枕叶出血，MRV示血栓形成。本文回顾了患者及其母亲有双侧下肢深静脉血栓形成史。基因检测显示患者及其两名家族成员携带PROS1杂合突变（c.751_752delAT, p.M251Vfs*17）。在24个月的随访研究中，患者持续接受利伐沙班治疗，恢复良好，mRS评分保持在2以下。凝血检查在正常范围内，MRV显示脑静脉窦部分再通。结论：PROS1基因（c.751_752delAT）的移框突变可能会严重影响蛋白S的功能，导致CVT的严重表型。利伐沙班对CVT合并遗传性血栓患者的治疗效果令人满意。
OBJECTIVE: To explore the clinical and prognostic features of CVT caused by PROS1 gene mutations and to provide clinical experience for new oral anticoagulants, such as rivaroxaban, in the treatment of CVT with a high risk of thrombosis.PATIENTS AND METHODS: The CVT patient's clinical symptoms were described, and the brain imaging and blood coagulation tests were performed to confirm the diagnosis of CVT. The patient's family members were recruited to receive blood coagulation tests and ultrasonic examination of lower limb vessels. Genetic analysis on the pedigree was carried out to identify the responsible gene for PS deficiency. We followed-up with this patient for 24 months to evaluate the clinical outcomes, laboratory results and imaging performances of CVT.RESULTS: The patient presented with typical CVT symptoms, including headache and epilepsy. Brain CT showed hemorrhage in the bilateral frontal lobe and left occipital lobe, while MRV demonstrated that thrombus had occurred. It was reviewed that the patient and his mother had a history of bilateral leg deep vein thrombosis. Gene tests revealed that the patient and two family members carried a heterozygous mutation of PROS1 (c.751_752delAT, p.M251Vfs*17). During 24 months of follow-up study, the patient was treated with rivaroxaban continuously and recovered well, supported by an mRS score that remained below 2. Blood coagulation tests were within normal limits, and MRV revealed partial recanalization of the cerebral venous sinus.CONCLUSIONS: The frame shift mutation in the PROS1 gene (c.751_752delAT) may greatly affect the function of protein S and lead to a severe phenotype of CVT. Rivaroxaban showed a satisfying therapeutic effect in this CVT patient with hereditary thrombophilia.