Fibrinogen Kanazawa: a congenital dysfibrinogenaemia with delayed polymerization having a replacement of proline-18 by leucine in the Aα-chain

Congenital dysfibrinogenaemia was found in a 39-year-old female and her two children. The proposita, apparently heterozygous for this abnormality, had no episode of bleeding or thrombosis. The abnormal fibrinogen showed normal release of fibrinopeptides A and B but impaired polymerization of the fibrin monomer. Amino acid sequence analysis of the whole Aα-chain isolated from fibrinogen Kanazawa showed a substitution of Leu for Pro at position 18 in the Aα-chain. This substitution was corroborated by the analysis of the amino acid sequence which demonstrated the lysyl endopeptidase peptides derived from the Aα-chain of fibrinogen Kanazawa. The minimal genetic exchange responsible for this substitution was a C±T transition in the middle position of the Pro codon. We condude that Pro-18 in the Aα-chain is crucial for the polymerization of the fibrin monomer.