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Borrell M.; Garí, M.; Coll, I.; Vallvé, C.; Tirado, I.; Soria, J. M.; Sala, N.; Muñoz, C.; Oliver, A.; García, A.; Fontcuberta, J.
Blood Coagulation & Fibrinolysis: May 1995
Research Papers: PDF Only

Congenital dysfibrinogenaemia was found in three non-related patients. None of them had a haemorrhagic tendency, but one gave a thrombotic history. When their fibrinogens were treated with thrombin, they released fibrinopeptides A and B at normal rates, but the resultant fibrin monomers produced exhibited abnormal polymerization curves. This abnormality was more marked in fibrinogen Villajoyosa than in Barcelonas III and IV. Plasminogen and t-PA binding to fibrin monomers from the three dysfibrinogenaemias was similar to that of normal fibrin monomers. The γ chain was purified from the three fibrinogens, treated with CNBr and the peptides produced were separated by reversed-phase HPLC. Chromatograms of digested fibrinogens showed an abnormal peak that was not present in the normal γ chain. Amino acid sequence analysis of abnormal peptides and genomic DNA sequencing revealed that the γ arginine 275 had been changed in the three fibrinogens; in two cases it was substituted by histidine, and in the third by cysteine. The altered properties observed in fibrin monomers produced from fibrinogen with the γArg 275→His or γArg 275→Cys substitution, suggests that this amino acid is important in maintaining the protein structure necessary for normal polymerization, but is not essential for the binding of t-PA or plasminogen to fibrin. It also suggests that the change Arg→Cys produces more severe alterations in the functions of fibrinogen than the substitution Arg→His.

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