Vaskulárna medicína 1/2021

Genetic background of von Willebrand disease

Introduction: Sequencing of a von Willebrand factor (vWF) gene provided new insights into the physiology of the vWF as well as its pathophysiology in the context of von Willebrand disease (vWD). In the 35 years since the sequence of the VWF gene was described, almost 600 mutations and a number of pathomechanisms that contribute to vWD have been identified. Aim: The article provides an overview of available information about the genetic background of vWD and our own experience with genetic testing of patients with vWD. Patients and methods: The study includes a laboratory diagnostics completed by genetic testing of the entire VWF gene of 27 patients with vWD. For genetic testing, we used a combination of next generation sequencing (NGS), Sanger sequencing and MLPA analysis. By combination of the mentioned genetic methods, we were able to identify 13 different genetic mutations, and thus explain the relationship between genotype and phenotype in most of the tested patients. Conclusion: Identification of mutations in patients with vWD helps to understand the cause of reduced plasma concentration or incorrect functional activity of vWF and explain the relationship between the identified genotype of a patient with vWD and its phenotype, clinical manifestations of the disease in terms of bleeding symptoms and influencing of individual laboratory parameters.

Keywords: von Willebrand disease, von Willebrand factor, genetic testing, mutation