fibrin and Down-Syndrome

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. Preoperative coagulation tests of his plasma revealed a prolonged thrombin time and the fibrinogen level determined by the thrombin time method was markedly decreased. Molecular weight of fibrinogen chains showed apparently normal A alpha-, B beta-, and gamma-chains. The rate of fibrinopeptide release was normal, whereas fibrin polymerization was delayed. Fibrinogen gamma-chain gene fragments from the propositus were amplified by polymerase chain reaction then sequenced. The triplet GAT, coding for the amino acid residue gamma 364, was replaced by CAT, resulting in the substitution of Asp-->His. This residue is adjacent to the Tyr-363 that is demonstrated to be the primary site for fibrin polymerization. Our results indicate that the residue gamma 364 Asp is essential for normal polymerization of fibrin monomer.

Topics: Asparagine; Blood Coagulation; Down Syndrome; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Histidine; Humans; Infant; Male; Point Mutation