FIBRINOGEN MATSUMOTO-I - A GAMMA-364 ASP-]HIS (GAT-]CAT) SUBSTITUTIONASSOCIATED WITH DEFECTIVE FIBRIN POLYMERIZATION

Fibrinogen Matsumoto I is a novel hereditary dysfibrinogen identified in a 1-year-old boy with Down's syndrome. Though he showed no apparent bleeding or thrombotic tendency, he had a congenital heart disease. P reoperative coagulation tests of his plasma revealed a prolonged throm bin time and the fibrinogen level determined by the thrombin time meth od was markedly decreased. Molecular weight of fibrinogen chains showe d apparently normal A alpha-, B beta-, and gamma-chains. The rate of f ibrinopeptide release was' normal, whereas fibrin polymerization was d elayed. Fibrinogen gamma-chain gene fragments from the propositus were amplified by polymerase chain reaction then sequenced. The tripler GA T, coding for the amino acid residue gamma 364, was replaced by CAT, r esulting in the substitution of Asp-->His. This residue is adjacent to the Tyr-363 that is demonstrated to be the primary site for fibrin po lymerization. Our results indicate that the residue gamma 364 Asp is e ssential for normal polymerization of fibrin monomer.