IngentaConnect Gene conversions are a common cause of von Willebrand disease

Authors: Gupta, P. K.¹; Adamtziki, E.²; Budde, U.³; Jaiprakash, M.¹; Kumar, H.¹; Harbeck-Seu, A.⁴; Kannan, M.⁵; Oyen, F.⁴; Obser, T.⁴; Wedekind, I.⁴; Saxena, R.⁵; Schneppenheim, R.⁴

Source: British Journal of Haematology, Volume 130, Number 5, September 2005 , pp. 752-758(7)

Publisher: Blackwell Publishing

Abstract:

Summary

von Willebrand disease (VWD), the most common inherited bleeding disorder, is very heterogeneous, both in its phenotype and genotype. One particular molecular mechanism of VWD is due to recombination events between the true gene and its pseudogene on chromosome 22. We assessed the frequency and extension of such events in 50 multi-ethnic index patients with severe VWD type 3 and in five index patients with VWD type 2M Vicenza. One additional unclassified patient had been diagnosed with possible VWD in Russia solely on a clinical basis. Gene conversions, previously thought to be rare events, were identified in >10% of our study population: in six multi-ethnic patients with severe VWD type 3, in one patient with VWD type 2M Vicenza and the Russian patient was finally diagnosed with VWD type 2B New York/Malmoe. Our results suggest a significant contribution of this particular molecular mechanism to the manifestation of VWD. The location of the gene conversions, their extension and their occurrence as homozygous, compound heterozygous or heterozygous mutations determines the resulting phenotype.

Keywords: gene conversion; type 3 von Willebrand disease; type 2M Vicenza; type 2B New York/Malmoe

Document Type: Research article

DOI: 10.1111/j.1365-2141.2005.05660.x

Affiliations: 1: Department of Transfusion Medicine, Armed Forces Medical College, Pune, India 2: Haemophilia–Haemostasis Unit, S. Aronis-Vournas, ‘Aghia Sophia’ Children's Hospital, Athens, Greece 3: Coagulation Laboratory, Lademannbogen, Hamburg, Germany 4: Department of Paediatric Haematology and Oncology, University Medical Centre Hamburg–Eppendorf, Hamburg, Germany 5: Department of Haematology, All India Institute of Medical Sciences, New Delhi, India

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