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This Article Full Text Full Text (PDF) 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 Attanasio, C. Articles by Neerman-Arbez, M. Search for Related Content PubMed PubMed Citation Articles by Attanasio, C. Articles by Neerman-Arbez, M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Gene Expression Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 March 2001, Vol. 97, No. 6, pp. 1879-1881 BRIEF REPORT Activation of multiple cryptic donor splice sites by the common congenital afibrinogenemia mutation, FGA IVS4 + 1 GT Catia Attanasio, Philippe de Moerloose, Stylianos E. Antonarakis, Michael A. Morris, and Marguerite Neerman-Arbez From the Division of Medical Genetics, University Medical School and University Hospital, Geneva, and the Division of Angiology and Hemostasis, University Hospital, Geneva, Switzerland. Our recent studies on the molecular basis of the autosomal recessive disorder congenital afibrinogenemia showed that the most common mutation is a donor splice mutation in FGA intron 4, IVS4 + 1 GT, accounting for approximately half of disease alleles. The effect of this mutation on messenger RNA (mRNA) splicing, however, remained unproven. COS-7 cells transfected with a normal plasmid construct produced 100% mRNA molecules with correct splicing, whereas cells transfected with a mutant construct produced multiple aberrant mRNAs, due to utilization of cryptic donor splice sites situated in exon 4 and intron 4. One particular site situated 4 base pairs (bp) downstream of the normal site was used in 85% of transcripts causing afibrinogenemia by a 4-bp insertion-frameshift, leading to premature alpha-chain truncation. Our results confirm the utility of transfecting COS-7 cells to study mRNA splice-site mutations and demonstrate that the common FGA IVS4 variant is a null mutation leading to afibrinogenemia. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Buratti, M. Chivers, J. Kralovicova, M. Romano, M. Baralle, A. R. Krainer, and I. Vorechovsky Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization Nucleic Acids Res., July 26, 2007; 35(13): 4250 - 4263. [Abstract] [Full Text] [PDF] 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] X. Roca, R. Sachidanandam, and A. R. Krainer Intrinsic differences between authentic and cryptic 5' splice sites Nucleic Acids Res., November 1, 2003; 31(21): 6321 - 6333. [Abstract] [Full Text] [PDF] K. Borensztajn, M.-L. Sobrier, A.-M. Fischer, O. Chafa, S. Amselem, and J. Tapon-Bretaudiere Factor VII gene intronic mutation in a lethal factor VII deficiency: effects on splice-site selection Blood, July 15, 2003; 102(2): 561 - 563. [Abstract] [Full Text] [PDF] C. Attanasio, A. David, and M. Neerman-Arbez Outcome of donor splice site mutations accounting for congenital afibrinogenemia reflects order of intron removal in the fibrinogen alpha gene (FGA) Blood, March 1, 2003; 101(5): 1851 - 1856. [Abstract] [Full Text] [PDF] S. Spena, S. Duga, R. Asselta, M. Malcovati, F. Peyvandi, and M. L. Tenchini Congenital afibrinogenemia: first identification of splicing mutations in the fibrinogen Bbeta -chain gene causing activation of cryptic splice sites Blood, December 15, 2002; 100(13): 4478 - 4484. [Abstract] [Full Text] [PDF] N. Okumura, F. Terasawa, H. Tanaka, M. Hirota, H. Ota, K. Kitano, K. Kiyosawa, and S. T. Lord Analysis of fibrinogen gamma -chain truncations shows the C-terminus, particularly gamma Ile387, is essential for assembly and secretion of this multichain protein Blood, May 15, 2002; 99(10): 3654 - 3660. [Abstract] [Full Text] [PDF] R. Asselta, S. Duga, S. Spena, E. Santagostino, F. Peyvandi, G. Piseddu, R. Targhetta, M. Malcovati, P. M. Mannucci, and M. L. Tenchini Congenital afibrinogenemia: mutations leading to premature termination codons in fibrinogen Aalpha -chain gene are not associated with the decay of the mutant mRNAs Blood, December 15, 2001; 98(13): 3685 - 3692. [Abstract] [Full Text] [PDF]

	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020