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Analysis of von Willebrand Disease in the “Heart of Europe”
Background von Willebrand disease (VWD) is a genetic bleeding disorder caused by defects of von Willebrand factor (VWF), quantitative (type 1 and 3) or qualitative (type 2). The laboratory phenotyping is heterogenic making diagnosis difficult. Objectives Complete laboratory analysis of VWD as an e...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Georg Thieme Verlag KG
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9581583/ https://www.ncbi.nlm.nih.gov/pubmed/36299619 http://dx.doi.org/10.1055/s-0042-1757635 |
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author | Vangenechten, Inge Smejkal, Petr Zavrelova, Jiri Zapletal, Ondrej Wild, Alexander Michiels, Jan Jacques Berneman, Zwi Blatny, Jan Batorova, Angelika Prigancova, Tatiana Penka, Miroslav Gadisseur, Alain |
author_facet | Vangenechten, Inge Smejkal, Petr Zavrelova, Jiri Zapletal, Ondrej Wild, Alexander Michiels, Jan Jacques Berneman, Zwi Blatny, Jan Batorova, Angelika Prigancova, Tatiana Penka, Miroslav Gadisseur, Alain |
author_sort | Vangenechten, Inge |
collection | PubMed |
description | Background von Willebrand disease (VWD) is a genetic bleeding disorder caused by defects of von Willebrand factor (VWF), quantitative (type 1 and 3) or qualitative (type 2). The laboratory phenotyping is heterogenic making diagnosis difficult. Objectives Complete laboratory analysis of VWD as an expansion of the previously reported cross-sectional family-based VWD study in the Czech Republic (BRNO-VWD) and Slovakia (BRA-VWD) under the name “Heart of Europe,” in order to improve the understanding of laboratory phenotype/genotype correlation. Patients and Methods In total, 227 suspected VWD patients were identified from historical records. Complete laboratory analysis was established using all available assays, including VWF multimers and genetic analysis. Results A total of 191 patients (from 119 families) were confirmed as having VWD. The majority was characterized as a type 1 VWD, followed by type 2. Multimeric patterns concordant with laboratory phenotypes were found in approximately 83% of all cases. A phenotype/genotype correlation was present in 84% (77% type 1, 99% type 2, and 61% type 3) of all patients. Another 45 candidate mutations (23 novel variations), not found in the initial study, could be identified (missense 75% and truncating 24%). An exon 1–3 gene deletion was identified in 14 patients where no mutation was found by direct DNA sequencing, increasing the linkage up to 92%, overall. Conclusion This study provides a cross-sectional overview of the VWD population in a part of Central Europe. It is an addition to the previously published BRNO-VWD study, and provides important data to the International Society of Thrombosis and Haemostasis/European Association for Haemophilia and Allied Disorders VWD mutation database with identification of novel causal mutations. |
format | Online Article Text |
id | pubmed-9581583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Georg Thieme Verlag KG |
record_format | MEDLINE/PubMed |
spelling | pubmed-95815832022-10-25 Analysis of von Willebrand Disease in the “Heart of Europe” Vangenechten, Inge Smejkal, Petr Zavrelova, Jiri Zapletal, Ondrej Wild, Alexander Michiels, Jan Jacques Berneman, Zwi Blatny, Jan Batorova, Angelika Prigancova, Tatiana Penka, Miroslav Gadisseur, Alain TH Open Background von Willebrand disease (VWD) is a genetic bleeding disorder caused by defects of von Willebrand factor (VWF), quantitative (type 1 and 3) or qualitative (type 2). The laboratory phenotyping is heterogenic making diagnosis difficult. Objectives Complete laboratory analysis of VWD as an expansion of the previously reported cross-sectional family-based VWD study in the Czech Republic (BRNO-VWD) and Slovakia (BRA-VWD) under the name “Heart of Europe,” in order to improve the understanding of laboratory phenotype/genotype correlation. Patients and Methods In total, 227 suspected VWD patients were identified from historical records. Complete laboratory analysis was established using all available assays, including VWF multimers and genetic analysis. Results A total of 191 patients (from 119 families) were confirmed as having VWD. The majority was characterized as a type 1 VWD, followed by type 2. Multimeric patterns concordant with laboratory phenotypes were found in approximately 83% of all cases. A phenotype/genotype correlation was present in 84% (77% type 1, 99% type 2, and 61% type 3) of all patients. Another 45 candidate mutations (23 novel variations), not found in the initial study, could be identified (missense 75% and truncating 24%). An exon 1–3 gene deletion was identified in 14 patients where no mutation was found by direct DNA sequencing, increasing the linkage up to 92%, overall. Conclusion This study provides a cross-sectional overview of the VWD population in a part of Central Europe. It is an addition to the previously published BRNO-VWD study, and provides important data to the International Society of Thrombosis and Haemostasis/European Association for Haemophilia and Allied Disorders VWD mutation database with identification of novel causal mutations. Georg Thieme Verlag KG 2022-10-19 /pmc/articles/PMC9581583/ /pubmed/36299619 http://dx.doi.org/10.1055/s-0042-1757635 Text en The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ) https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Vangenechten, Inge Smejkal, Petr Zavrelova, Jiri Zapletal, Ondrej Wild, Alexander Michiels, Jan Jacques Berneman, Zwi Blatny, Jan Batorova, Angelika Prigancova, Tatiana Penka, Miroslav Gadisseur, Alain Analysis of von Willebrand Disease in the “Heart of Europe” |
title | Analysis of von Willebrand Disease in the “Heart of Europe” |
title_full | Analysis of von Willebrand Disease in the “Heart of Europe” |
title_fullStr | Analysis of von Willebrand Disease in the “Heart of Europe” |
title_full_unstemmed | Analysis of von Willebrand Disease in the “Heart of Europe” |
title_short | Analysis of von Willebrand Disease in the “Heart of Europe” |
title_sort | analysis of von willebrand disease in the “heart of europe” |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9581583/ https://www.ncbi.nlm.nih.gov/pubmed/36299619 http://dx.doi.org/10.1055/s-0042-1757635 |
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