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Semin Thromb Hemost 2020; 46(04): 484-500
DOI: 10.1055/s-0039-3402430
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Genetic Background of von Willebrand Disease: History, Current State, and Future Perspectives

Jana Zolkova
1   Department of Hematology and Transfusiology, National Centre of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Martin University Hospital, Comenius University in Bratislava, Martin, Slovakia
,
Juraj Sokol
1   Department of Hematology and Transfusiology, National Centre of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Martin University Hospital, Comenius University in Bratislava, Martin, Slovakia
,
Tomas Simurda
1   Department of Hematology and Transfusiology, National Centre of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Martin University Hospital, Comenius University in Bratislava, Martin, Slovakia
,
Lubica Vadelova
1   Department of Hematology and Transfusiology, National Centre of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Martin University Hospital, Comenius University in Bratislava, Martin, Slovakia
,
Zuzana Snahnicanova
2   Division of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia
,
Dusan Loderer
2   Division of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia
,
Miroslava Dobrotova
1   Department of Hematology and Transfusiology, National Centre of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Martin University Hospital, Comenius University in Bratislava, Martin, Slovakia
,
Jela Ivankova
1   Department of Hematology and Transfusiology, National Centre of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Martin University Hospital, Comenius University in Bratislava, Martin, Slovakia
,
Ingrid Skornova
1   Department of Hematology and Transfusiology, National Centre of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Martin University Hospital, Comenius University in Bratislava, Martin, Slovakia
,
Zora Lasabova
2   Division of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia
,
Peter Kubisz
1   Department of Hematology and Transfusiology, National Centre of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Martin University Hospital, Comenius University in Bratislava, Martin, Slovakia
,
Jan Stasko
1   Department of Hematology and Transfusiology, National Centre of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Martin University Hospital, Comenius University in Bratislava, Martin, Slovakia
› Institutsangaben Funding Our work on VWD is supported by grants VEGA1/0187/17, VEGA 1/0168/16, and APVV 16–0020.
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Publikationsverlauf

Publikationsdatum:
30. Dezember 2019 (online)

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Abstract

Sequencing of the gene encoding for von Willebrand factor (VWF) has brought new insight into the physiology of VWF as well as its pathophysiology in the context of von Willebrand disease (VWD). Molecular testing in VWD patients has shown high variability in the overall genetic background of this condition. Almost 600 mutations and many disease-causing mechanisms have been described in the 35 years since the VWF gene was identified. Genetic testing in VWD patients is now available in many centers as a part of the VWD diagnostic algorithm. Molecular mechanisms leading to types 2 and 3 VWD are well characterized; thus, information from genetic analysis in these VWD types may be beneficial for their correct classification. However, the molecular basis of type 1 VWD is still not fully elucidated and most likely represents a multifactorial disorder reflecting a combined impact of environmental and genetic factors within and outside of VWF. Regarding sequencing methods, the previous gold-standard Sanger sequencing is gradually being replaced with next-generation sequencing methods that are more cost- and time-effective. Instead of gene-by-gene approaches, gene panels of genes for coagulation factors and related proteins have recently become a center of attention in patients with inherited bleeding disorders, especially because a high proportion of VWD patients, mainly those with low VWF plasma levels (type 1), appear to be free of mutations in VWF. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) are accessible in a very limited number of laboratories. Results from these studies have presented several genes other than VWF or ABO possibly affecting VWF levels, and such findings will need further validation studies.

Keywords

von Willebrand disease - von Willebrand factor - genetic background - genetic testing
 

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