Molecular basis and thrombotic manifestations of antithrombin deficiency in 15 unrelated Chinese patients
Molecular basis and thrombotic manifestations of antithrombin deficiency in 15 unrelated Chinese patients
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15 例无亲属关系的中国患者抗凝血酶缺乏症的分子基础和血栓表现。
DOI：
10.1016/j.thromres.2013.07.013
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发表时间：
2013-09-01
影响因子：
7.5
通讯作者：
Wang, Hongli
中科院分区：
文献类型：
--
作者：
Ding, Qiulan;Wang, Min;Wang, Hongli
简介：抗凝血酶（AT）缺乏与血栓形成的风险增加。材料和方法：15例无血缘关系的AT缺乏的患者，由血栓形成试验定义和详细的临床资料，对患者的个人和家族史的血栓栓塞（TE），重点记录。结果：共检测出15个杂合突变，每个突变发生在一个家系中。首次报道了5个突变（33.3%），其中3个无效突变（Ser 36 X、Lys 70 X和Try 307 X）和2个错义突变（Phe 123 Cys和Leu 340 Phe），AT结构分析表明，这些突变可能影响蛋白质的结构完整性和稳定性。在15例患者中，33.3%（5/15）有其他风险因素，仅1例患者存在导致血栓形成早发的其他遗传变异。14例患者（93.9%）在首次血栓形成后发生多部位复发性血栓形成。93.3%的患者出现深静脉血栓形成（DVT），40.0%的患者出现肠系膜静脉血栓形成（MVT）。此外，两名无关患者均出现静脉和动脉血栓形成。在15个无血缘关系的家系中，AT缺乏者发生TE事件的发生率为51.0%。结论：AT缺乏者应采取预防性抗凝措施，以避免血栓的复发和多部位血栓的发生。原发性MVT和AT缺陷的关联被强调。(C)2013爱思唯尔有限公司保留所有权利。
Introduction: Antithrombin (AT) deficiency is associated with an increasing risk of thrombosis.Materials and methods: 15 unrelated patients with AT deficiency defined by thrombophilic assays were recruited and detailed clinical information about patients, focusing on the personal and family history of thromboembolism (TE), were recorded. Mutation analysis was performed by direct sequencing of an AT gene (SERPINC1) in the patients and their family members.Results: A total of 15 heterozygous causative mutations, each being identified in one family, were identified. Five mutations (33.3%) were reported here for the first time, including three null mutations (Ser36X, Lys70X and Try307X) and two missense mutations (Phe123Cys and Leu340Phe) probably impairing the structural integrity and stability of protein based on the AT structural analysis. Of the 15 patients, 33.3% (5/15) had additional risk factors and only one patient presented with additional genetic alteration causing an early onset of thrombosis. Fourteen patients (93.9%) suffered from multisite recurrent thrombotic episodes after a first episode of thrombosis. 93.3% of the patients experienced deep vein thrombosis (DVT) and 40.0% presented with mesenteric venous thrombosis (MVT). In addition, both venous and arterial thrombosis was present in two unrelated patients. 51.0% subjects with AT deficiency in the 15 unrelated pedigrees experienced TE events.Conclusions: Prophylactic anticoagulation may be suggested in AT-deficient patients to avoid the recurrent and multisite thrombosis. The association of primary MVT and AT deficiency is highlighted. (C) 2013 Elsevier Ltd. All rights reserved.