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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3162-3168. Prepublished online as a Blood First Edition Paper on January 4, 2005; DOI 10.1182/blood-2004-04-1621. This Article Full Text (PDF) All Versions of this Article: 2004-04-1621v1 105/8/3162    most recent Alert me when this article is cited Alert me if a correction is posted 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 Keller, M. A Articles by Weisel, J. W Search for Related Content PubMed PubMed Citation Articles by Keller, M. A Articles by Weisel, J. W Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 28, 2004 Accepted December 10, 2004 Fibrinogen Philadelphia, a hypodysfibrinogenemia characterized by abnormal polymerization and fibrinogen hypercatabolism due to S378P mutation Margaret A Keller, Jose Martinez, Timothy C Baradet, Chandrasekaran Nagaswami, Irina N Chernysh, Meggin K Borowski, Saul Surrey, and John W Weisel* Division of Hematology and Cardeza Foundation for Hematologic Research, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA * Corresponding author; email: weisel{at}cellbio.med.upenn.edu. Fibrinogen Philadelphia, a hypodysfibrinogenemia described in a family with a history of bleeding 1, is characterized by prolonged thrombin time, abnormal fibrin polymerization and increased catabolism of the abnormal fibrinogen. Turbidity studies of polymerization of purified fibrinogen under different ionic conditions reveal a reduced lag period and lower final turbidity, indicating more rapid initial polymerization and impaired lateral aggregation. Consistent with this, scanning and transmission electron microscopy show fibers with substantially lower average fiber diameters. DNA sequence analysis of the fibrinogen genes A, B and G revealed a T C transition in exon 9 resulting in a serine to proline substitution near the chain C-terminus (S378P). The S378P mutation is associated with fibrinogen Philadelphia in this kindred and was not found in 10 controls. This region of the chain is involved in fibrin polymerization, supporting this as the polymerization defect-causing mutation. Thus, this abnormal fibrinogen is characterized by two unique features; 1) abnormal polymerization probably due to a major defect in lateral aggregation; and, 2) hypercatabolism of the mutant protein. The location, nature and unusual characteristics of this mutation may add to our understanding of fibrinogen protein interactions necessary for normal catabolism and fibrin formation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. A. Dugan, V. W.-C. Yang, D. J. McQuillan, and M. Hook Decorin Modulates Fibrin Assembly and Structure J. Biol. Chem., December 15, 2006; 281(50): 38208 - 38216. [Abstract] [Full Text] [PDF]

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