{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T21:43:22Z","timestamp":1793742202161,"version":"4.6.1"},"reference-count":81,"publisher":"American Society of Hematology","issue":"15","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Type 3 von Willebrand disease (VWD3) is a rare and severe bleeding disorder characterized by often undetectable von Willebrand factor (VWF) plasma levels, a recessive inheritance pattern, and heterogeneous genotype. The objective of this study was to identify the VWF defects in 265 European and Iranian patients with VWD3 enrolled in 3WINTERS-IPS (Type 3 Von Willebrand International Registries Inhibitor Prospective Study). All analyses were performed in centralized laboratories. The VWF genotype was studied in 231 patients with available DNA (121 [115 families] from Europe [EU], and 110 [91 families] from Iran [IR]). Among 206 unrelated patients, 134 were homozygous (EU\/IR = 57\/77) and 50 were compound heterozygous (EU\/IR = 43\/7) for VWF variants. In 22 patients, no or only one variant was found. A total of 154 different VWF variants (EU\/IR = 101\/58 [5 shared]) were identified among the 379 affected alleles (EU\/IR = 210\/169), of which 48 (EU\/IR = 18\/30) were novel. The variants p.Arg1659*, p.Arg1853*, p.Arg2535*, p.Cys275Ser, and delEx1_Ex5 were found in both European and Iranian VWD3 patients. Sixty variants were identified only in a single allele (EU\/IR = 50\/10), whereas 18 were recurrent (\u22653 patients) within 144 affected alleles. Nine large deletions and one large insertion were found. Although most variants predicted null alleles, 21% of patients carried at least 1 missense variant. VWD3 genotype was more heterogeneous in the European population than in the Iranian population, with nearly twice as many different variants. A higher number of novel variants were found in the Iranian VWD3 patients.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020003397","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T16:56:03Z","timestamp":1628182563000},"page":"2987-3001","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":33,"title":["Genotypes of European and Iranian patients with type 3 von Willebrand disease enrolled in 3WINTERS-IPS"],"prefix":"10.1182","volume":"5","author":[{"given":"Luciano","family":"Baronciani","sequence":"first","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Peake","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Schneppenheim","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University Medical Centre, Hamburg-Eppendorf, Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Goodeve","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoo","family":"Ahmadinejad","sequence":"additional","affiliation":[{"name":"Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran;"},{"name":"Pediatric Congenital Hematologic Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Badiee","sequence":"additional","affiliation":[{"name":"Hemophilia-Thalassemia Center, Mashhad University of Medical Science, Mashad, Islamic Republic of Iran;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad-Reza","family":"Baghaipour","sequence":"additional","affiliation":[{"name":"Iranian Hemophilia Comprehensive Treatment Centre, Tehran, Islamic Republic of Iran;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2883-9049","authenticated-orcid":false,"given":"Olga","family":"Benitez","sequence":"additional","affiliation":[{"name":"Hemophilia Unit, University Vall d\u2019Hebron Hospital, Barcelona, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imre","family":"Bod\u00f3","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Hematology\u2013Semmelweis University, Budapest, Hungary;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Budde","sequence":"additional","affiliation":[{"name":"Hemostaseology Medilys Laborgesellschaft mbH, Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Cairo","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Castaman","sequence":"additional","affiliation":[{"name":"Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Florence, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3503-1363","authenticated-orcid":false,"given":"Peyman","family":"Eshghi","sequence":"additional","affiliation":[{"name":"Pediatric Congenital Hematologic Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Goudemand","sequence":"additional","affiliation":[{"name":"Univ. Lille, CHU Lille, Haematology and Transfusion, Lille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolf","family":"Hassenpflug","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University Medical Centre, Hamburg-Eppendorf, Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid","family":"Hoorfar","sequence":"additional","affiliation":[{"name":"Hemophilia Center, Esfahan University of Medical Science, Esfahan, Islamic Republic of Iran;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehran","family":"Karimi","sequence":"additional","affiliation":[{"name":"Hematology Research Center, Shiraz University of Medical Science, Shiraz, Iran;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijan","family":"Keikhaei","sequence":"additional","affiliation":[{"name":"Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1911-3094","authenticated-orcid":false,"given":"Riitta","family":"Lassila","sequence":"additional","affiliation":[{"name":"Research Program Unit in Oncology, University of Helsinki, Helsinki University Central Hospital, Coagulation Disorders, Helsinki, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank W. 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