Hampshire, D.J. orcid.org/0000-0002-1387-8926, Abuzenadah, A.M., Cartwright, A. et al. (10 more authors) (2013) Identification and characterisation of mutations associated with von Willebrand disease in a Turkish patient cohort. Thrombosis and Haemostasis, 110 (2). pp. 264-274. ISSN 0340-6245
Abstract
Several cohort studies have investigated the molecular basis of von Willebrand disease (VWD); however, these have mostly focused on European and North American populations. This study aimed to investigate mutation spectrum in 26 index cases (IC) from Turkey diagnosed with all three VWD types, the majority (73%) with parents who were knowingly related. IC were screened for mutations using multiplex ligation-dependent probe amplification and analysis of all von Willebrand factor gene (VWF) exons and exon/intron boundaries. Selected missense mutations were expressed in vitro. Candidate VWF mutations were identified in 25 of 26 IC and included propeptide missense mutations in four IC (two resulting in type 1 and two in recessive 2A), all influencing VWF expression in vitro. Four missense mutations, a nonsense mutation and a small in-frame insertion resulting in type 2A were also identified. Of 15 type 3 VWD IC, 13 were homozygous and two compound heterozygous for 14 candidate mutations predicted to result in lack of expression and two propeptide missense changes. Identification of intronic breakpoints of an exon 17–18 deletion suggested that the mutation resulted from non-homologous end joining. This study provides further insight into the pathogenesis of VWD in a population with a high degree of consanguineous partnerships.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2013 Schattauer. This is an author produced version of a paper subsequently published in Thrombosis and Haemostasis. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | von Willebrand disease; mutation analysis; Large-scale deletion; multiplex ligation-dependent probe amplification; recessive 2A |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection, Immunity and Cardiovascular Disease The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 01 Mar 2017 13:03 |
Last Modified: | 23 Mar 2018 08:39 |
Published Version: | https://doi.org/10.1160/TH13-02-0135 |
Status: | Published |
Publisher: | Schattauer |
Refereed: | Yes |
Identification Number: | 10.1160/TH13-02-0135 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:110834 |