{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:51:15Z","timestamp":1791244275378,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,2,20]],"date-time":"2017-02-20T00:00:00Z","timestamp":1487548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006396","name":"Alexion Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006396","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:p>The role of molecular characterization in the diagnosis of von Willebrand disease (<jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content>) is not essential if the patients have been extensively investigated using phenotypic analysis. On the other hand, if some of these phenotype assays are not available, the identification of the mutation causing the disease could be crucial for an accurate diagnosis. Nevertheless, there are several reasons for performing molecular analysis in patients phenotypically well characterized, e.g. to identify the mutation causing <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content> can be useful for patients and their family members when prenatal diagnosis is required (type 3 or severe type 2). In this manuscript, we report the techniques used for the molecular characterization of suspected <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content> patients. We describe the use of online von Willebrand factor database and online single nucleotide variation databases, the former to verify whether a candidate mutation has been previously identified in other <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content> patients and the latter to ascertain whether a putative mutation has been reported earlier in healthy individuals. We listed the available <jats:italic>in silico<\/jats:italic> analysis tools, to determine the predicted pathogenicity of a sequence variant and to establish its possible negative effect on the normal splicing process. We also report the strategy that can be used to identify <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content> type 2 patients' mutations in subjects who have been fully characterized using the phenotype assays.<\/jats:p>","DOI":"10.1111\/hae.13175","type":"journal-article","created":{"date-parts":[[2017,2,21]],"date-time":"2017-02-21T17:09:22Z","timestamp":1487696962000},"page":"188-197","source":"Crossref","is-referenced-by-count":39,"title":["Molecular diagnosis of von Willebrand disease"],"prefix":"10.1111","volume":"23","author":[{"given":"L.","family":"Baronciani","sequence":"first","affiliation":[{"name":"Angelo Bianchi Bonomi Hemophilia and Thrombosis Center Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Luigi Villa Foundation Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Goodeve","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity and Cardiovascular Disease University of Sheffield Medical School Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7423-9864","authenticated-orcid":false,"given":"F.","family":"Peyvandi","sequence":"additional","affiliation":[{"name":"Angelo Bianchi Bonomi Hemophilia and Thrombosis Center Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Luigi Villa Foundation Milan Italy"},{"name":"Department of Pathophysiology and Transplantation Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01643.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112974"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4613-0331-2_7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03482.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03670.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03765.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)47144-5"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00215a036"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00359a014"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-405134"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0204692"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00399a013"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1987.tb02591.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1182\/blood.V96.5.1808","article-title":"von Willebrand factor storage and multimerization: 2 independent intracellular processes","volume":"96","author":"Haberichter SL","year":"2003","journal-title":"Blood"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000017063.36768.87"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-06-528406"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.012336"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.04060.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04204.x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.055285"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH15-04-0282"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH15-07-0604"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08400.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02078.x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31816b5cae"},{"key":"e_1_2_9_27_1","unstructured":"WallisY PayneS McAnultyCet al.Practice Guidelines for the Evaluation of Pathogenicity and the Reporting of Sequence Variants in Clinical Molecular Genetics 2013. 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