Review ArticleVon Willebrand disease mutation spectrum and associated mutation mechanisms

- Von Willebrand disease is mainly caused by mutations in von Willebrand factor.
- Over 750 unique mutations in von Willebrand factor have been reported so far.
- Mutation mechanisms have been studied for many von Willebrand factor mutations.
- This review describes an overview of the von Willebrand factor mutation mechanisms.

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.