Division of Hematology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Clin Invest. 2013 Sep;123(9):3710-2. doi: 10.1172/JCI71220. Epub 2013 Aug 27.
In a report reading like a fascinating detective story, Vincent and colleagues crack the mysterious case of east Texas bleeding disorder. They show that affected individuals have a mutation in exon 13 of the coagulation F5 gene that causes increased expression of an alternatively spliced transcript, which encodes a previously unrecognized factor V (FV) isoform they call FV-short. This FV isoform lacks a large portion of the B domain of FV, which is normally released upon the proteolytic activation of FV by thrombin and binds tightly to the coagulation regulator tissue factor pathway inhibitor-α (TFPIα). This interaction leads to an approximately 10-fold increase in the level of TFPIα circulating in plasma and a resultant anticoagulant effect that produces a hemorrhagic diathesis.
在一篇读起来像引人入胜的侦探故事的报告中，Vincent 及其同事破解了得克萨斯州东部出血性疾病的神秘病例。他们表明，受影响的个体在凝血因子 F5 基因的外显子 13 中存在突变，导致一种经过剪接的转录本表达增加，该转录本编码一种以前未被识别的因子 V（FV）异构体，他们称之为 FV-short。这种 FV 异构体缺乏 FV 的 B 结构域的大部分，该结构域通常在凝血酶对 FV 的蛋白水解激活时释放，并与凝血调节剂组织因子途径抑制剂-α（TFPIα）紧密结合。这种相互作用导致 TFPIα 在血浆中循环水平增加约 10 倍，并产生抗凝作用，从而导致出血倾向。
