Genetic analysis should be included in clinical practice when screening for antithrombin deficiency
Genetic analysis should be included in clinical practice when screening for antithrombin deficiency
复制标题
筛查抗凝血酶缺乏症时，应将遗传分析纳入临床实践
DOI：
10.1160/th14-05-0446
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发表时间：
2015-02-01
影响因子：
6.7
通讯作者：
Hu, Yu
中科院分区：
文献类型：
--
作者：
Zeng, Wei;Tang, Liang;Hu, Yu
抗凝血酶（AT）缺乏会增加血栓形成的风险。目前的证据表明，一些负责抗凝血酶缺乏症的SERPINC1突变往往呈现轻微降低或正常的活性，因此无法通过功能测试检测到。本研究旨在比较活性测定和直接遗传分析在识别遗传性抗凝血酶缺乏症。总共入组了400例静脉血栓形成的连续患者。功能检测显示，400人中有16人的抗凝血酶活性降低，其中14人通过遗传分析得到证实。在剩下的384名患者中，95名没有已知危险因素的个体和95名有易感因素的个体也被选择进行基因测序。在9个个体中发现了另外8个致病突变，它们也应该被认为是抗凝血酶缺乏症。此外，一个复发性突变，p.Arg356_Phe361del，进行了表征。该突变体似乎具有部分受损的分泌和功能活性降低50%。这项研究表明，包括遗传分析的筛选试验，以确定抗凝血酶缺乏症是必不可少的。具体而言，强烈建议当个体经历无端血栓性疾病时，即使AT活动正常，也要进行SERPINC1的遗传分析。
Summary Antithrombin (AT) deficiency increases the risk of thrombosis. Current evidence shows that some SERPINC1 mutations responsible for antithrombin deficiency often present a slightly decreased or normal activity and therefore could not be detected by functional tests. This study was designed to compare activity assays and direct genetic analyses in identifying hereditary antithrombin deficiency. In total, 400 consecutive patients with venous thrombosis were enrolled. Functional assays showed that 16 of the 400 individuals had decreased antithrombin activity, and 14 of them were confirmed by genetic analysis. Of the remaining 384 patients, 95 individuals without a known risk factor and 95 individuals with predisposing factors were also selected for gene sequencing. Eight additional causative mutations were identified in nine individuals and they should also be considered as antithrombin deficiency. In addition, a recurrent mutation, p.Arg356_Phe361del, was characterised. The mutant appeared to have a partially impaired secretion and a reduction in functional activity by 50 %. This study indicated that including genetic analysis in screening tests for identifying antithrombin deficiency was essential. Specifically, a genetic analysis of SERPINC1 is strongly recommended when individuals experience unprovoked thrombotic diseases, even if the AT activities are normal.