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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 (PDF) 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 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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 5, 2006 Accepted July 18, 2006 The mutational spectrum of type 1 von Willebrand disease: results from a Canadian cohort study Paula D. James, Colleen Notley, Carol Hegadorn, Jayne Leggo, Angie Tuttle, Shawn Tinlin, Christine Brown, Chandler Andrews, Andrea Labelle, Yvette Chirinian, Lee O'Brien, Maha Othman, Georges Rivard, Dilys Rapson, Christine Hough, and David Lillicrap* Dept of Medicine & Dept of Pathology & Molecular Medicine, Queen's University, Kingston, Canada Dept of Pathology & Molecular Medicine, Queen's University, Kingston, Canada Hopital Sainte-Justine * Corresponding author; email: lillicrap{at}cliff.path.queensu.ca. In order to evaluate the changes within the VWF gene that might contribute to the pathogenesis of Type 1 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 supports 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?

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