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Identification and characterisation of mutations associated with von Willebrand disease in a Turkish patient cohort

Hampshire, Daniel J.; Abuzenadah, Adel M.; Cartwright, Ashley; Al-Shammari, Nawal S.; Coyle, Rachael E.; Eckert, Michaela; Al-Buhairan, Ahlam M.; Messenger, Sarah L.; Budde, Ulrich; Gürsel, Türkiz; Ingerslev, Jørgen; Peake, Ian R.; Goodeve, Anne C.


Adel M. Abuzenadah

Ashley Cartwright

Nawal S. Al-Shammari

Rachael E. Coyle

Michaela Eckert

Ahlam M. Al-Buhairan

Sarah L. Messenger

Ulrich Budde

Türkiz Gürsel

Jørgen Ingerslev

Ian R. Peake

Anne C. Goodeve


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 mu tations, 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. © Schattauer 2013.


Hampshire, D. J., Abuzenadah, A. M., Cartwright, A., Al-Shammari, N. S., Coyle, R. E., Eckert, M., …Goodeve, A. C. (2013). Identification and characterisation of mutations associated with von Willebrand disease in a Turkish patient cohort. Thrombosis and haemostasis, 110(2), 264-274.

Journal Article Type Article
Publication Date Aug 13, 2013
Deposit Date May 24, 2022
Journal Thrombosis and Haemostasis
Print ISSN 0340-6245
Publisher Schattauer
Peer Reviewed Peer Reviewed
Volume 110
Issue 2
Pages 264-274
Keywords Large-scale deletion; Multiplex ligation-dependent probe amplification; Mutation analysis; Recessive 2A; von Willebrand disease
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