Randi A M, Sacchi E, Castaman G C, Rodeghiero F, Mannucci P M
A. Bianchi Bonomi Hemophilia and Thrombosis Centre, IRCCS Maggiore Hospital, Milano, Italy.
Thromb Haemost. 1993 Feb 1;69(2):173-6.
Type I von Willebrand disease (vWD) Vicenza is a rare variant with autosomal dominant transmission, characterized by the presence of supranormal von Willebrand factor (vWF) multimers in plasma, similar to those normally found in endothelial cells and megakaryocytes. The patients have very low levels of plasma vWF contrasting with a mild bleeding tendency. The pathophysiology of this subtype is still unknown. The presence of supranormal multimers in the patients' plasma could be due to a mutation in the vWF molecule which affects post-translational processing, or to a defect in the cells' processing machinery, independent of the vWF molecule. In order to determine if type I vWD Vicenza is linked to the vWF gene, we studied six polymorphic systems identified within the vWF gene in two apparently unrelated families with type I vWD Vicenza. The results of this study indicate a linkage between vWF gene and the type I vWD Vicenza trait. This strongly suggests that type I vWD Vicenza is due to a mutation in one of the vWF alleles, which results in an abnormal vWF molecule that is processed to a lesser extent than normal vWF.
I型威勒布兰德病（vWD）维琴察型是一种罕见的常染色体显性遗传变异型，其特征是血浆中存在超正常的血管性血友病因子（vWF）多聚体，类似于正常在内皮细胞和巨核细胞中发现的多聚体。患者血浆vWF水平极低，但出血倾向较轻。该亚型的病理生理学仍不清楚。患者血浆中存在超正常多聚体可能是由于vWF分子发生影响翻译后加工的突变，或者是细胞加工机制存在缺陷，与vWF分子无关。为了确定I型vWD维琴察型是否与vWF基因相关，我们在两个明显无亲缘关系的I型vWD维琴察型家族中研究了vWF基因内鉴定出的六个多态系统。这项研究结果表明vWF基因与I型vWD维琴察型特征之间存在连锁关系。这强烈提示I型vWD维琴察型是由于vWF等位基因之一发生突变，导致vWF分子异常，其加工程度低于正常vWF。
