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Prepublished online as a Blood First Edition Paper on April 3, 2003; DOI 10.1182/blood-2002-09-2951. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-09-2951v1 102/2/561    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Borensztajn, K. Articles by Tapon-Bretaudiére, J. Search for Related Content PubMed PubMed Citation Articles by Borensztajn, K. Articles by Tapon-Bretaudiére, J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 July 2003, Vol. 102, No. 2, pp. 561-563 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief report Factor VII gene intronic mutation in a lethal factor VII deficiency: effects on splice-site selection Keren Borensztajn, Marie-Laure Sobrier, Anne-Marie Fischer, Ouerdia Chafa, Serge Amselem, and Jacqueline Tapon-Bretaudiére From the Institut National de la Santé et de la Recherche Médicale (INSERM) U428, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris V, Paris, France; Hôpital Européen Georges Pompidou, Laboratoire d'Hématologie, Paris, France; INSERM U468, Hôpital Henri Mondor, Créteil, France; and CHU Mustapha, Alger, Algeria In a patient with lethal factor VII (FVII) deficiency, 2 homozygous nucleotide substitutions were identified in the F7 gene: a IVS7+2T>G transversion involving the IVS7 donor splice site, followed by a mutation at nucleotide 10588 that would result in a missense variation (Arg224Gln). The mutated splice site, located within the first repeat of a minisatellite, is followed by a variable number of pseudo-sites, normally silent. To investigate the consequences of this mutation on F7 splicing, we designed normal and mutant minigenes, spanning exons 5 to 8. In cells transfected with the mutant construct, no normal splicing occurred. Only spliced transcripts including the first minisatellite repeat were observed, resulting from the activation of the most proximal wild-type pseudo-site, which would generate a truncated protein (stop codon upstream of nucleotide 10588). These findings, which suggest the existence of a mechanism selecting one single splice site among multiple cryptic sites, explain the patient's phenotype. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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