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Blood, 15 April 2004, Vol. 103, No. 8, pp. 3051-3054. Prepublished online as a Blood First Edition Paper on December 24, 2003; DOI 10.1182/blood-2003-10-3725. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-10-3725v1 103/8/3051    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 Asselta, R. Articles by Tenchini, M. L. Search for Related Content PubMed PubMed Citation Articles by Asselta, R. Articles by Tenchini, M. L. Related Collections Hemostasis, Thrombosis, and Vascular Biology Gene Expression Brief Reports Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief report Missense or splicing mutation? The case of a fibrinogen B-chain mutation causing severe hypofibrinogenemia Rosanna Asselta, Stefano Duga, Silvia Spena, Flora Peyvandi, Giancarlo Castaman, Massimo Malcovati, Pier Mannuccio Mannucci, and Maria Luisa Tenchini From the Department of Biology and Genetics for Medical Sciences, University of Milan, Milan, Italy; Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Department of Internal Medicine, University of Milan and IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Maggiore Hospital, Milan, Italy; Department of Hematology and Hemophilia and Thrombosis Center, San Bortolo Hospital, Vicenza, Italy. The genetic basis of severe hypofibrinogenemia was analyzed in a 57-year-old Italian woman. She turned out to be a compound heterozygote for a novel putative missense mutation (Leu172Gln) and a previously described nonsense mutation (Arg17Stop) in the fibrinogen B-chain gene. The pathogenetic role of Leu172Gln was analyzed by in vitro expression of the mutant recombinant protein in COS-1 cells. These experiments demonstrated that mutant B-Leu172Gln fibrinogen was normally assembled and secreted. Inspection of the nucleotide sequence surrounding the mutation suggested a possible role on pre–messenger RNA (mRNA) splicing. Production of the mutant transcript in HeLa cells confirmed that the mutation activates a cryptic acceptor splice site in exon 4, resulting in a truncated B chain, lacking approximately 70% of the C-terminal region. This represents the first exonic splicing mutation identified in the fibrinogen genes. These findings strengthen the importance to analyze potentially pathogenetic nucleotide variations at both the protein and the mRNA level. (Blood. 2004; 103:3051-3054) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Fibrinogen faux pas Victor J. Marder Blood 2004 103: 2867-2868. [Full Text] [PDF] This article has been cited by other articles: S. Spena, M. L. Tenchini, and E. Buratti Cryptic splice site usage in exon 7 of the human fibrinogen B{beta}-chain gene is regulated by a naturally silent SF2/ASF binding site within this exon RNA, June 1, 2006; 12(6): 948 - 958. [Abstract] [Full Text] [PDF] J. Kralovicova, M. B. Christensen, and I. Vorechovsky Biased exon/intron distribution of cryptic and de novo 3' splice sites Nucleic Acids Res., September 1, 2005; 33(15): 4882 - 4898. [Abstract] [Full Text] [PDF] P. D. James, L. A. O'Brien, C. A. Hegadorn, C. R. P. Notley, G. D. Sinclair, C. Hough, M.-C. Poon, and D. Lillicrap A novel type 2A von Willebrand factor mutation located at the last nucleotide of exon 26 (3538G>A) causes skipping of 2 nonadjacent exons Blood, November 1, 2004; 104(9): 2739 - 2745. [Abstract] [Full Text] [PDF]

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