{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T06:21:19Z","timestamp":1771654879387,"version":"3.50.1"},"reference-count":91,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union under European Regional Development Fund","award":["GINOP-2.3.2-15-2016-00039"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00039"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Diagnosis of rare bleeding disorders is challenging and there are several differential diagnostics issues. Next-generation sequencing (NGS) is a useful tool to overcome these problems. The aim of this study was to demonstrate the usefulness of molecular genetic investigations by summarizing the diagnostic work on cases with certain bleeding disorders. Here we report only those, in whom NGS was indicated due to uncertainty of diagnosis or if genetic confirmation of initial diagnosis was required. Based on clinical and\/or laboratory suspicion of von Willebrand disease (vWD, n = 63), hypo-or dysfibrinogenemia (n = 27), hereditary hemorrhagic telangiectasia (HHT, n = 10) and unexplained activated partial thromboplastin time (APTT) prolongation (n = 1), NGS using Illumina platform was performed. Gene panel covered 14 genes (ACVRL1, ENG, MADH4, GDF2, RASA1, F5, F8, FGA, FGB, FGG, KLKB1, ADAMTS13, GP1BA and VWF) selected on the basis of laboratory results. We identified forty-seven mutations, n = 29 (6 novel) in vWD, n = 4 mutations leading to hemophilia A, n = 10 (2 novel) in fibrinogen disorders, n = 2 novel mutations in HHT phenotype and two mutations (1 novel) leading to prekallikrein deficiency. By reporting well-characterized cases using standardized, advanced laboratory methods we add new pieces of data to the continuously developing \u201cbleeding disorders databases\u201d, which are excellent supports for clinical patient management.<\/jats:p>","DOI":"10.3390\/life11030202","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T05:03:15Z","timestamp":1614920595000},"page":"202","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Resolving Differential Diagnostic Problems in von Willebrand Disease, in Fibrinogen Disorders, in Prekallikrein Deficiency and in Hereditary Hemorrhagic Telangiectasia by Next-Generation Sequencing"],"prefix":"10.3390","volume":"11","author":[{"given":"R\u00e9ka","family":"Gindele","sequence":"first","affiliation":[{"name":"Division of Clinical Laboratory Science and Specialist Clinical Hemostasis Laboratory, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrienne","family":"Ker\u00e9nyi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Department of Laboratory Medicine, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judit","family":"K\u00e1llai","sequence":"additional","affiliation":[{"name":"Division of Clinical Laboratory Science and Specialist Clinical Hemostasis Laboratory, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gy\u00f6rgy","family":"Pfliegler","sequence":"additional","affiliation":[{"name":"Center of Expertise for Rare Diseases, Clinical Center, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1gota","family":"Schlammadinger","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Istv\u00e1n","family":"Szegedi","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2114-2935","authenticated-orcid":false,"given":"Tam\u00e1s","family":"Major","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology and Head-Neck Surgery Division, Ken\u00e9zy Gyula Teaching Hospital, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zsuzsanna","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Division of Clinical Laboratory Science and Specialist Clinical Hemostasis Laboratory, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5314-5607","authenticated-orcid":false,"given":"Zsuzsa","family":"Bagoly","sequence":"additional","affiliation":[{"name":"Division of Clinical Laboratory Science and Specialist Clinical Hemostasis Laboratory, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5170-5965","authenticated-orcid":false,"given":"Csongor","family":"Kiss","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e1nos","family":"Kappelmayer","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1483-3703","authenticated-orcid":false,"given":"Zsuzsanna","family":"Bereczky","sequence":"additional","affiliation":[{"name":"Division of Clinical Laboratory Science and Specialist Clinical Hemostasis Laboratory, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"ref_1","unstructured":"(2021, January 23). 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