Department of Internal Medicine, Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Department of Internal Medicine, Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Thromb Res. 2017 Nov;159:65-75. doi: 10.1016/j.thromres.2017.09.025. Epub 2017 Sep 23.
Von Willebrand disease (VWD) is a bleeding disorder that is mainly caused by mutations in the multimeric protein von Willebrand factor (VWF). These mutations may lead to deficiencies in plasma VWF or dysfunctional VWF. VWF is a heterogeneous protein and over the past three decades, hundreds of VWF mutations have been identified. In this review we have organized all reported mutations, spanning a timeline from the late eighties until early 2017. This resulted in an overview of 750 unique mutations that are divided over the VWD types 1, 2A, 2B, 2M, 2N and 3. For many of these mutations the disease-causing effects have been characterized in vitro through expression studies, ex vivo by analysis of patient-derived endothelial cells, as well as in animal or (bio)physical models. Here we describe the mechanisms associated with the VWF mutations per VWD type.
血管性血友病（VWD）是一种出血性疾病，主要由多聚体蛋白血管性血友病因子（VWF）的突变引起。这些突变可能导致血浆 VWF 缺乏或 VWF 功能障碍。VWF 是一种异质性蛋白，在过去的三十年中，已经发现了数百种 VWF 突变。在这篇综述中，我们整理了所有已报道的突变，跨越了从 80 年代末到 2017 年初的时间线。这导致了 750 种独特突变的概述，这些突变分为 1、2A、2B、2M、2N 和 3 型 VWD。对于这些突变中的许多突变，已经通过体外表达研究、通过对患者来源的内皮细胞的分析（离体）以及在动物或（生物）物理模型中对其致病作用进行了描述。在这里，我们按 VWD 类型描述与 VWF 突变相关的机制。
