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Blood, 1 January 2007, Vol. 109, No. 1, pp. 145-154. Prepublished online as a Blood First Edition Paper on August 10, 2006; DOI 10.1182/blood-2006-05-021105. This Article Full Text Full Text (PDF) Supplemental Appendix Supplemental Appendix All Versions of this Article: blood-2006-05-021105v1 109/1/145    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 Citing Articles via Google Scholar Google Scholar Articles by James, P. D. Articles by Lillicrap, D. Search for Related Content PubMed PubMed Citation Articles by James, P. D. Articles by Lillicrap, D. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Free Research Articles Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The mutational spectrum of type 1 von Willebrand disease: results from a Canadian cohort study Paula D. James1,2, Colleen Notley2, Carol Hegadorn2, Jayne Leggo2, Angie Tuttle2, Shawn Tinlin2, Christine Brown2, Chandler Andrews2, Andrea Labelle2, Yvette Chirinian2, Lee O'Brien2, Maha Othman2, Georges Rivard3, Dilys Rapson2, Christine Hough2, David Lillicrap, for the Association of Hemophilia Clinic Directors of Canada2, 1 Department of Medicine and 2 Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada; and 3 Hôpital Sainte-Justine, Montreal, QC, Canada In order to evaluate the changes within the VWF gene that might contribute to the pathogenesis of type 1 von Willebrand disease (VWD), a large multicenter Canadian study was undertaken. We present data from the sequence analysis of the VWF gene in 123 type 1 VWD index cases and their families. We have identified putative mutations within the VWF gene in 63% (n = 78) of index cases, leaving 37% (n = 45) with no identified changes. These changes comprise 50 different putative mutations: 31 (62%) missense mutations, 8 (16%) changes involving the VWF transcriptional regulatory region, 5 (10%) small deletions/insertions, 5 (10%) splicing consensus sequence mutations, and 1 nonsense mutation. Twenty-one of the index cases had more than one putative VWF mutation identified. We were somewhat more likely to identify putative mutations in cases with lower VWF levels, and the contribution of other factors, such as ABO blood group, seems more important in milder cases. Taken as a whole, our data support a complex spectrum of molecular pathology resulting in type 1 VWD. In more severe cases, genetic changes are common within the VWF gene and are highly penetrant. In milder cases, the genetic determinants are more complex and involve factors outside of the VWF gene. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. F. De Meyer, H. 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Haberichter, G. Castaman, U. Budde, I. Peake, A. Goodeve, F. Rodeghiero, A. B. Federici, J. Batlle, D. Meyer, C. Mazurier, et al. Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: Molecular and Clinical Markers for the Diagnosis and Management of Type 1 VWD (MCMDM-1VWD) Blood, May 15, 2008; 111(10): 4979 - 4985. [Abstract] [Full Text] [PDF] G. Castaman, S. Lethagen, A. B. Federici, A. Tosetto, A. Goodeve, U. Budde, J. Batlle, D. Meyer, C. Mazurier, E. Fressinaud, et al. Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD Blood, April 1, 2008; 111(7): 3531 - 3539. [Abstract] [Full Text] [PDF] What Is Type 1 von Willebrand Disease? Journal Watch Oncology and Hematology, January 22, 2007; 2007(122): 5 - 5. [Full Text] R. R. Montgomery Mouse VWF again teaches us diversity of mechanisms Blood, November 1, 2006; 108(9): 2887 - 2887. [Full Text] [PDF]

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