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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4671-4673. Prepublished online as a Blood First Edition Paper on February 22, 2005; DOI 10.1182/blood-2004-05-1864. This Article Full Text (PDF) All Versions of this Article: 2004-05-1864v1 105/12/4671    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kravtsov, D. V Articles by Gailani, D. Search for Related Content PubMed PubMed Citation Articles by Kravtsov, D. V Articles by Gailani, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 17, 2004 Accepted February 16, 2005 A classification system for cross-reactive material negative factor XI deficiency Dmitri V Kravtsov, Paul E Monahan, and David Gailani* Department of Pathology, Vanderbilt University, Nashville, TN, USA Department of Pediatrics, University of North Carolina-Chapel Hill School of Medicine, Chapel Hill, NC, USA Department of Pathology, Vanderbilt University, Nashville, TN, USA; Department of Medicine, Vanderbilt University, Nashville, TN, USA * Corresponding author; email: dave.gailani{at}vanderbilt.edu. The bleeding disorder associated with factor XI (fXI) deficiency is typically inherited as an autosomal recessive trait. However, some fXI mutations may be associated with dominant disease transmission. FXI is a homodimer, a feature that could allow certain mutations to exert a dominant negative effect on wild type fXI secretion through heterodimer formation. We describe two novel fXI mutations (Ser225Phe and Cys398Tyr) that form intracellular dimers, are secreted poorly, and exhibit dominant negative effects on wild type fXI secretion in co-transfection experiments. Available data now suggest that mutations associated with cross reactive material negative fXI deficiency fall into one of three mechanistic categories: (1) mutations that reduce or prevent polypeptide synthesis, (2) polypeptides that fail to form intracellular dimers and are retained in cells as monomers, and (3) polypeptides that form dimers that are not secreted. The latter category likely accounts for many cases of dominant disease transmission. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Zadra, R. Asselta, M. L. Tenchini, G. Castaman, U. Seligsohn, P. M. Mannucci, and S. Duga Simultaneous genotyping of coagulation factor XI type II and type III mutations by multiplex real-time polymerase chain reaction to determine their prevalence in healthy and factor XI-deficient Italians Haematologica, May 1, 2008; 93(5): 715 - 721. [Abstract] [Full Text] [PDF] M. Zucker, A. Zivelin, M. Landau, O. Salomon, G. Kenet, F. Bauduer, M. Samama, J. Conard, M.-H. Denninger, A.-S. Hani, et al. Characterization of seven novel mutations causing factor XI deficiency Haematologica, October 1, 2007; 92(10): 1375 - 1380. [Abstract] [Full Text] [PDF]

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