{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:30:41Z","timestamp":1790501441611,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T00:00:00Z","timestamp":1568764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Type 3 von Willebrand disease (VWD), a severe autosomal recessive hereditary bleeding disorder, is described by the virtual absence of von Willebrand factor (VWF). In consanguineous populations, for example Pakistan, the disease is reported with a higher incidence rate than the worldwide prevalence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>This study aims to characterize molecular pathology and clinical profile of type 3 VWD cohort of Pakistani origin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In total, 48 patients were enrolled in the current study. Initially, the index patients (IPs) were evaluated by a standardized questionnaire for recording bleeding manifestations and by performing conventional coagulation tests. The diagnosis of VWD type 3 was confirmed by VWF antigens less than 5\u00a0IU\/dL. Direct sequencing of VWF gene (<jats:italic>VWF)<\/jats:italic> was carried out to identify causative gene variations. We evaluated the potential consequence of novel splice site and missense variations by predictive computational programs and in silico structural analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>VWF<\/jats:italic> mutations were detected in 46 out of 48 IPs (95.8%), predominantly as homozygous variants. In total, twenty\u2010nine different gene defects were characterized in this cohort from which 10 (34.5%) are novel. The majority of the mutations were null alleles (66%; including gene conversions, nonsense, splice site variations, small deletions and insertions), and 34% of them were missense substitutions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Herein, we reported for the first time, the pattern of gene defects in Pakistani type 3 VWD cohort. We identified a wide heterogeneous mutation spectrum along with variability in the type of bleeding episodes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.13841","type":"journal-article","created":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T16:41:21Z","timestamp":1568824881000},"page":"1035-1044","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Characterization of the mutation spectrum in a Pakistani cohort of type 3 von Willebrand disease"],"prefix":"10.1111","volume":"25","author":[{"given":"Shariq","family":"Ahmed","sequence":"first","affiliation":[{"name":"National Institute of Blood Disease &amp; Bone Marrow Transplantation Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2006-8497","authenticated-orcid":false,"given":"Hamideh","family":"Yadegari","sequence":"additional","affiliation":[{"name":"Institute of Experimental Haematology and 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