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Blood, 30 July 2009, Vol. 114, No. 5, pp. 1091-1098. Prepublished online as a Blood First Edition Paper on April 16, 2009; DOI 10.1182/blood-2008-08-173278. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-08-173278v1 114/5/1091    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Sutherland, M. S. Articles by Keeney, S. PubMed PubMed Citation Articles by Sutherland, M. S. Articles by Keeney, S. Related Collections Thrombosis and Hemostasis Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  THROMBOSIS AND HEMOSTASIS A novel deletion mutation is recurrent in von Willebrand disease types 1 and 3 Megan S. Sutherland1, Anthony M. Cumming1, Mackenzie Bowman2, Paula H. B. Bolton-Maggs1, Derrick J. Bowen3, Peter W. Collins3, Charles R. M. Hay1, Andrew M. Will4, and Stephen Keeney1 1 University Department of Haematology, Manchester Royal Infirmary, Manchester, United Kingdom; 2 Pathology and Molecular Medicine, Queen's University, Kingston, ON; 3 Department of Haematology, School of Medicine, Cardiff University, Cardiff, United Kingdom; and 4 Department of Haematology, Royal Manchester Children's Hospital, Manchester, United Kingdom Direct sequencing of VWF genomic DNA in 21 patients with type 3 von Willebrand disease (VWD) failed to reveal a causative homozygous or compound heterozygous VWF genotype in 5 cases. Subsequent analysis of VWF mRNA led to the discovery of a deletion (c.221-977_532 + 7059del [p.Asp75_Gly178del]) of VWF in 7 of 12 white type 3 VWD patients from 6 unrelated families. This deletion of VWF exons 4 and 5 was absent in 9 patients of Asian origin. We developed a genomic DNA-based assay for the deletion, which also revealed its presence in 2 of 34 type 1 VWD families, segregating with VWD in an autosomal dominant fashion. The deletion was associated with a specific VWF haplotype, indicating a possible founder origin. Expression studies indicated markedly decreased secretion and defective multimerization of the mutant VWF protein. Further studies have found the mutation in additional type 1 VWD patients and in a family expressing both type 3 and type 1 VWD. The c.221-977_532 + 7059del mutation represents a previously unreported cause of both types 1 and 3 VWD. Screening for this mutation in other type 1 and type 3 VWD patient populations is required to elucidate further its overall contribution to VWD arising from quantitative deficiencies of VWF. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: When 1 plus 1 equals 3 in VWD Anne C. Goodeve Blood 2009 114: 933-934. [Abstract] [Full Text] [PDF] This article has been cited by other articles: A. C. Goodeve When 1 plus 1 equals 3 in VWD Blood, July 30, 2009; 114(5): 933 - 934. [Abstract] [Full Text] [PDF]

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