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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 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 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 Kravtsov, D. V. Articles by Gailani, D. Search for Related Content PubMed PubMed Citation Articles by Kravtsov, D. V. Articles by Gailani, D. Related Collections Hemostasis, Thrombosis, and Vascular Biology Brief Reports Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief report A classification system for cross-reactive material-negative factor XI deficiency Dmitri V. Kravtsov, Paul E. Monahan, and David Gailani From the Department of Pathology, Vanderbilt University, Nashville, TN; the Department of Medicine, Vanderbilt University, Nashville, TN; and the Department of Pediatrics, University of North Carolina, Chapel Hill School of Medicine, Chapel Hill. 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 2 novel fXI mutations (Ser225Phe and Cys398Tyr) that form intracellular dimers, are secreted poorly, and exhibit dominant-negative effects on wild-type fXI secretion in cotransfection experiments. Available data now suggest that mutations associated with crossreactive material-negative fXI deficiency fall into 1 of 3 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. (Blood. 2005;105: 4671-4673) 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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