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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 Pinotti, M. Articles by Bernardi, F. Search for Related Content PubMed PubMed Citation Articles by Pinotti, M. Articles by Bernardi, F. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 92 No. 5 (September 1), 1998: pp. 1646-1651 Molecular Mechanisms of FVII Deficiency: Expression of Mutations Clustered in the IVS7 Donor Splice Site of Factor VII Gene M. Pinotti, R. Toso, R. Redaelli, M. Berrettini, G. Marchetti, and F. Bernardi From the Dipartimento di Biochimica e Biologia Molecolare - CIBF, Sezione SBPGU, Università di Ferrara, Ferrara; the Divisione di Ematologia, Ospedale Niguarda, Milano; and the Istituto di Medicina Interna e di Medicina Vascolare, Università di Perugia, Perugia, Italy. In three Italian patients, two point mutations and a short deletion were found in the intron 7 of factor VII gene, clustered in the donor splice site and located in the first of several repeats. The mutation 9726+5GA, the most frequent cause of symptomatic factor VII deficiency in Italy, as well as the deletion (9729del4) gave rise in expression studies to abnormally spliced transcripts, which were exclusively produced from the cryptic site in the second repeat. The insertion in the mature mRNA of the first intronic repeat caused (9726+5GA) a reading frameshift, abolishing most of the factor VII catalytic domain, or produced (9729del4), an altered factor with 11 additional residues, the activity of which was not detectable in the cell medium after mutagenesis and expression studies. Studies of factor VII ectopic mRNA from leukocytes and expression studies indicated that the deleted gene produced 30% of normally spliced transcript. Differently, the 9726+5GA mutation permitted a very low level (0.2% to 1%) of correct splicing to occur, which could be of great importance to prevent the onset, in the homozygous patients, of most of the life-threatening bleeding symptoms. The 9726+7AG mutation was found to be a rare and functionally silent polymorphism. These findings, which provide further evidence of the interplay of sequence and position in the 5 splice site selection, throw light on the heterogeneous molecular bases and clinical phenotypes of FVII deficiency. © 1998 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: M. Pinotti, L. Rizzotto, D. Balestra, M. A. Lewandowska, N. Cavallari, G. Marchetti, F. Bernardi, and F. Pagani U1-snRNA-mediated rescue of mRNA processing in severe factor VII deficiency Blood, March 1, 2008; 111(5): 2681 - 2684. [Abstract] [Full Text] [PDF] E. Castoldi, J. W. P. Govers-Riemslag, M. Pinotti, D. Bindini, G. Tans, M. Berrettini, M. G. Mazzucconi, F. Bernardi, and J. Rosing Coinheritance of Factor V (FV) Leiden enhances thrombin formation and is associated with a mild bleeding phenotype in patients homozygous for the FVII 9726+5G>A (FVII Lazio) mutation Blood, December 1, 2003; 102(12): 4014 - 4020. [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] M. I. Rees, T. M. Lewis, J. B. J. Kwok, G. R. Mortier, P. Govaert, R. G. Snell, P. R. Schofield, and M. J. Owen Hyperekplexia associated with compound heterozygote mutations in the {beta}-subunit of the human inhibitory glycine receptor (GLRB) Hum. Mol. Genet., April 1, 2002; 11(7): 853 - 860. [Abstract] [Full Text] [PDF] M. Pinotti, D. Etro, D. Bindini, M. L. Papa, G. Rodorigo, A. Rocino, G. Mariani, N. Ciavarella, and F. Bernardi Residual factor VII activity and different hemorrhagic phenotypes in CRM+ factor VII deficiencies (Gly331Ser and Gly283Ser) Blood, February 15, 2002; 99(4): 1495 - 1497. [Abstract] [Full Text] [PDF] M. Pinotti, R. Toso, D. Girelli, D. Bindini, P. Ferraresi, M. L. Papa, R. Corrocher, G. Marchetti, and F. Bernardi Modulation of factor VII levels by intron 7 polymorphisms: population and in vitro studies Blood, June 1, 2000; 95(11): 3423 - 3428. [Abstract] [Full Text] [PDF]

	Copyright © 1998 by American Society of Hematology         Online ISSN: 1528-0020