{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T18:51:33Z","timestamp":1793904693625,"version":"4.8.0"},"reference-count":36,"publisher":"BMJ","issue":"1","funder":[{"DOI":"10.13039\/501100017170","name":"Thailand Science Research and Innovation","doi-asserted-by":"publisher","award":["4390675"],"award-info":[{"award-number":["4390675"]}],"id":[{"id":"10.13039\/501100017170","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2023,10,28]]},"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Von Willebrand disease (VWD) is an inherited haemostatic disorder with a wide range of bleeding phenotypes based on von Willebrand factor (VWF) levels. Multiple assays including <jats:italic>VWF<\/jats:italic> gene analysis are employed to correctly diagnose VWD and its subtypes. However, data on <jats:italic>VWF<\/jats:italic> mutations among Southeast Asian populations are lacking. We, therefore, aimed to explore genetic variations in Thai patients with type 2 and type 3 VWD by whole exome sequencing (WES).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this multicentre study, Thai patients with type 2 and type 3 VWD, according to the definitions and VWF levels recommended by the international guidelines, were recruited. WES was performed using DNA extracted from peripheral blood in all cases. The novel variants were verified by Sanger sequencing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Fifteen patients (73% females; median age at diagnosis 3.0 years) with type 2 (n=12) and type 3 VWD (n=3) from 14 families were enrolled. All patients harboured at least one <jats:italic>VWF<\/jats:italic> variant. Six missense (p.Arg1374Cys, p.Arg1374His, p.Arg1399Cys, p.Arg1597Trp, p.Ser1613Pro, p.Pro1648Arg) and one splice-site (c.3379+1G&gt;A) variants in the <jats:italic>VWF<\/jats:italic> gene were formerly described. Notably, six <jats:italic>VWF<\/jats:italic> variants, including three missense (p.Met814Ile, p.Trp856Cys, p.Pro2032Leu), one deletion (c.2251delG) and two splice-site (c.7729+4A&gt;C, c.8115+2delT) mutations were novelly identified. Compound heterozygosity contributed to type 2 and type 3 VWD phenotypes in two and one patients, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Type 2 and type 3 VWD in Thailand demonstrate the mutational variations among <jats:italic>VWF<\/jats:italic> exons\/introns with several unique variants. The WES-based approach potentially provides helpful information to verify VWD diagnosis and facilitate genetic counselling in clinical practice.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jcp-2023-209123","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T13:21:05Z","timestamp":1700659265000},"page":"57-63","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic variations of type 2 and type 3 von Willebrand diseases in Thailand"],"prefix":"10.1136","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2432-8022","authenticated-orcid":false,"given":"Supanun","family":"Lauhasurayotin","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand"},{"name":"Integrative and Innovative Hematology\/Oncology Research Unit, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6257-0867","authenticated-orcid":false,"given":"Chatphatai","family":"Moonla","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand"},{"name":"Center of Excellence in Translational Hematology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7540-7564","authenticated-orcid":false,"given":"Rungnapa","family":"Ittiwut","sequence":"additional","affiliation":[{"name":"Center of Excellence for Medical Genomics, Medical Genomics Cluster, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand"},{"name":"Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7238-589X","authenticated-orcid":false,"given":"Chupong","family":"Ittiwut","sequence":"additional","affiliation":[{"name":"Center of Excellence for Medical Genomics, Medical Genomics Cluster, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand"},{"name":"Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9336-6682","authenticated-orcid":false,"given":"Natsaruth","family":"Songthawee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla, 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