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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 McVey, J. H. Articles by Tuddenham, E. G.D. Search for Related Content PubMed PubMed Citation Articles by McVey, J. H. Articles by Tuddenham, E. G.D. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 92 No. 3 (August 1), 1998: pp. 920-926 Exclusion of the First EGF Domain of Factor VII by a Splice Site Mutation Causes Lethal Factor VII Deficiency John H. McVey, Emma J. Boswell, Osamu Takamiya, Gabriel Tamagnini, Victor Valente, Teresa Fidalgo, Mark Layton, and Edward G.D. Tuddenham From the Haemostasis Research Group, MRC Clinical Sciences Centre, ICSM, London, UK; the School of Allied Medical Science, Shinshu University, Matsumoto, Japan; Servico de Hematologia, Centro Hospitalar de Coimbra, Coimbra, Portugal; and the Department of Haematological Medicine, King's College Hospital, London, UK. We have studied a family with homozygous lethal, blood coagulation factor VII (FVII) deficiency. To identify the mutation responsible for the deficiency, exons 2 to 8 and the intron-exon junctions of their FVII genes were amplified from peripheral white blood cell DNA by polymerase chain reaction and screened by single-strand conformational polymorphism analysis. The fragment showing aberrant mobility was cloned and sequenced. We detected a single point mutation, a homozygous G to A substitution at nucleotide position 6070, in the invariant GT dinucleotide at the 5 splice site of intron 4. Homozygosity was confirmed by loss of a site for the restriction endonuclease Mlu I. Analysis of the splicing pattern of ectopic transcripts in lymphocytes in the parents revealed that this mutation is associated with skipping of exon 4, which produces an mRNA encoding FVII with an in-frame deletion of the first epidermal growth factor-like domain (EGF 1). Transient transfection of COS-7 cells with an expression vector containing the EGF 1 FVII cDNA shows that this mutant protein is not expressed. The identification of the molecular basis of the FVII deficiency in this family allowed mutation-specific prenatal diagnosis to be performed in a subsequent pregnancy. In this family complete FVII deficiency is associated with a severe bleeding diathesis but no developmental abnormalities, lending weight to the hypothesis that fetal FVII is not required for the putative angiogenic functions of tissue factor in humans. © 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: L.-C. Yu, Y.-C. Twu, C.-Y. Chang, and M. Lin Molecular Basis of the Kell-null Phenotype. A MUTATION AT THE SPLICE SITE OF HUMAN KEL GENE ABOLISHES THE EXPRESSION OF KELL BLOOD GROUP ANTIGENS J. Biol. Chem., March 23, 2001; 276(13): 10247 - 10252. [Abstract] [Full Text] [PDF]

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