Hypoglycosylation is a common finding in antithrombin deficiency in the absence of a SERPINC1 gene defect
Hypoglycosylation is a common finding in antithrombin deficiency in the absence of a SERPINC1 gene defect
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DOI：
10.1111/jth.13372
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发表时间：
2016-08-01
影响因子：
10.4
通讯作者：
Vicente, V.
中科院分区：
文献类型：
--
作者：
de la Morena-Barrio, M. E.;Martinez-Martinez, I.;Vicente, V.
背景自从抗凝血酶缺陷被发现以来，50年前，很少有新的嗜血栓性缺陷被发现，所有这些缺陷的血栓形成风险都低于抗凝血酶缺陷。结果高比例的患者（8/30：27%）有低糖基化形式的抗凝血酶升高。在这些患者中检测的所有N-糖蛋白（1-抗胰蛋白酶、FXI和转铁蛋白）的电泳、HPLC和Q-TOF图谱与先天性糖基化疾病（罕见隐性多系统疾病）的图谱难以区分。然而，除一人外，所有人都没有精神残疾。此外，间歇性抗凝血酶缺乏症和低糖基化记录在这8名患者中的5名，所有与适度饮酒。遗传分析，包括全外显子组测序，揭示了参与N-糖基化pathway.Conclusions的不同基因的突变，我们的研究提供了大量的和新的机制的见解两种疾病的过程，诊断和临床护理的潜在影响。异常的N-糖基化导致隐性或短暂的抗凝血酶缺陷是一种新的血栓形成倾向。我们的数据表明，先天性糖基化障碍可能被低估，特别是在以血栓形成为主要或唯一临床表现的病例中。
Background Since the discovery of antithrombin deficiency, 50 years ago, few new thrombophilic defects have been identified, all with weaker risk of thrombosis than antithrombin deficiency.Objective To identify new thrombophilic mechanisms.Patients/methods We studied 30 patients with antithrombin deficiency but no defects in the gene encoding this key anticoagulant (SERPINC1).Results A high proportion of these patients (8/30: 27%) had increased hypoglycosylated forms of antithrombin. All N-glycoproteins tested in these patients (1-antitrypsin, FXI and transferrin) had electrophoretic, HPLC and Q-TOF patterns indistinguishable from those of the congenital disorders of glycosylation (rare recessive multisystem disorders). However, all except one had no mental disability. Moreover, intermittent antithrombin deficiency and hypoglycosylation was recorded in five out of these eight patients, all associated with moderate alcohol intake. Genetic analysis, including whole exome sequencing, revealed mutations in different genes involved in the N-glycosylation pathway.Conclusions Our study provides substantial and novel mechanistic insights into two disease processes, with potential implications for diagnosis and clinical care. An aberrant N-glycosylation causing a recessive or transient antithrombin deficiency is a new form of thrombophilia. Our data suggest that congenital disorders of glycosylation are probably underestimated, especially in cases with thrombosis as the main or only clinical manifestation.