Global prevalence of platelet-type von Willebrand disease
Background: Platelet-type von Willebrand disease (PT-VWD) is a rare autosomal dominant disorder. It is caused by gain-of-function gene variants in the platelet GP1BA, which results in excessive binding between GPIbα and von Willebrand factor (VWF). The prevalence of PT-VWD is unknown. Objectives: To...
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Elsevier
2025-01-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2475037925000068 |
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| author | Omid Seidizadeh Andrea Cairo Maha Othman Flora Peyvandi |
| author_facet | Omid Seidizadeh Andrea Cairo Maha Othman Flora Peyvandi |
| author_sort | Omid Seidizadeh |
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| description | Background: Platelet-type von Willebrand disease (PT-VWD) is a rare autosomal dominant disorder. It is caused by gain-of-function gene variants in the platelet GP1BA, which results in excessive binding between GPIbα and von Willebrand factor (VWF). The prevalence of PT-VWD is unknown. Objectives: To establish the worldwide and within distinct ethnic groups prevalence of PT-VWD. Methods: We used available exome and genome sequencing data of 807,162 (730,947 exomes and 76,215 genomes) subjects from the Genome Aggregation Database (gnomAD-v4.1). Results: Among the 1,614,324 alleles analyzed in the gnomAD population, there were 1397 distinct GP1BA variants. Of them, 4 variants (p.Arg127Gln, p.Leu194Phe, p.Gly249Val, and p.Met255Ile) have been previously reported to cause PT-VWD. Considering these 4 known pathogenic variants, we estimated a global PT-VWD prevalence of 136 cases/106. The highest estimated prevalence of PT-VWD was found in Africans/African Americans (160/106), Finnish (156/106), Europeans (149/106), and South Asians (110/106), followed by Ashkenazi Jewish (68/106) and East Asian (45/106) ethnicities. In the population with no assigned ethnicity, a prevalence of 126/106 was estimated. Since no pathogenic GP1BA variants that were previously reported to cause PT-VWD were found in Admixed American and Middle Eastern ethnicities, we were unable to estimate the PT-VWD prevalence in these 2 populations. We found a global prevalence of 2.5/106 for severe PT-VWD and 134/106 for the mild form. Conclusion: This population-based genetic epidemiology analysis indicates a substantially higher than expected frequency of PT-VWD. This novel finding suggests that a large number of PT-VWD patients are still under- or misdiagnosed. |
| format | Article |
| id | doaj-art-c1d59a7ea0a049ca935ebdc227918bd5 |
| institution | Kabale University |
| issn | 2475-0379 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj-art-c1d59a7ea0a049ca935ebdc227918bd52025-02-02T05:29:09ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-01-0191102682Global prevalence of platelet-type von Willebrand diseaseOmid Seidizadeh0Andrea Cairo1Maha Othman2Flora Peyvandi3Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, ItalyFondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, ItalyDepartment of Biomedical & Molecular Sciences, Queen's University, Kingston, Ontario, CanadaDepartment of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy; Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy; Correspondence Flora Peyvandi, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Via Pace 9, 20122 Milan, Italy.Background: Platelet-type von Willebrand disease (PT-VWD) is a rare autosomal dominant disorder. It is caused by gain-of-function gene variants in the platelet GP1BA, which results in excessive binding between GPIbα and von Willebrand factor (VWF). The prevalence of PT-VWD is unknown. Objectives: To establish the worldwide and within distinct ethnic groups prevalence of PT-VWD. Methods: We used available exome and genome sequencing data of 807,162 (730,947 exomes and 76,215 genomes) subjects from the Genome Aggregation Database (gnomAD-v4.1). Results: Among the 1,614,324 alleles analyzed in the gnomAD population, there were 1397 distinct GP1BA variants. Of them, 4 variants (p.Arg127Gln, p.Leu194Phe, p.Gly249Val, and p.Met255Ile) have been previously reported to cause PT-VWD. Considering these 4 known pathogenic variants, we estimated a global PT-VWD prevalence of 136 cases/106. The highest estimated prevalence of PT-VWD was found in Africans/African Americans (160/106), Finnish (156/106), Europeans (149/106), and South Asians (110/106), followed by Ashkenazi Jewish (68/106) and East Asian (45/106) ethnicities. In the population with no assigned ethnicity, a prevalence of 126/106 was estimated. Since no pathogenic GP1BA variants that were previously reported to cause PT-VWD were found in Admixed American and Middle Eastern ethnicities, we were unable to estimate the PT-VWD prevalence in these 2 populations. We found a global prevalence of 2.5/106 for severe PT-VWD and 134/106 for the mild form. Conclusion: This population-based genetic epidemiology analysis indicates a substantially higher than expected frequency of PT-VWD. This novel finding suggests that a large number of PT-VWD patients are still under- or misdiagnosed.http://www.sciencedirect.com/science/article/pii/S2475037925000068gnomADGP1BAplatelet disordersprevalencePT-VWDVWD |
| spellingShingle | Omid Seidizadeh Andrea Cairo Maha Othman Flora Peyvandi Global prevalence of platelet-type von Willebrand disease Research and Practice in Thrombosis and Haemostasis gnomAD GP1BA platelet disorders prevalence PT-VWD VWD |
| title | Global prevalence of platelet-type von Willebrand disease |
| title_full | Global prevalence of platelet-type von Willebrand disease |
| title_fullStr | Global prevalence of platelet-type von Willebrand disease |
| title_full_unstemmed | Global prevalence of platelet-type von Willebrand disease |
| title_short | Global prevalence of platelet-type von Willebrand disease |
| title_sort | global prevalence of platelet type von willebrand disease |
| topic | gnomAD GP1BA platelet disorders prevalence PT-VWD VWD |
| url | http://www.sciencedirect.com/science/article/pii/S2475037925000068 |
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