Characterization of fibrinogen Milano I: Amino acid exchange γ330Asp → Val impairs fibrin polymerization

P. Reber, M. Furlan, C. Rupp, M. Kehl, A. Henschen, P. M. Mannucci, E. A. Beck

Research output: Contribution to journalArticlepeer-review


An abnormal fibrinogen was found in two asymptomatic members (father and daughter) of the same family, originating from northern Italy. Routine coagulation studies revealed prolonged thrombin and reptilase clotting times. Plasma fibrinogen levels, as determined by a functional assay, were markedly diminished, whereas the heat precipitation method indicated normal fibrinogen values. On the basis of these findings, a tentative diagnosis of dysfibrinogenemia was made, and according to the accepted nomenclature, this fibrinogen variant was called 'fibrinogen Milano I'. The time course of fibrinopeptide A and B release from fibrinogen Milano I was normal, but the aggregation of fibrin monomers was delayed. Two-dimensional electrophoresis of reduced variant fibrinogen chains showed a defective γ-chain with increased cathodic mobility. An abnormal electrophoretic mobility was observed also for the γ-chain remnants of fibrinogen fragments D1 and D2 derived from fibrinogen Milano I, whereas the charge anomaly was lost after a further digestion by plasmin to D3, suggesting that the structure abnormality of this variant is situated in the region γ303-356. An abnormal peptide was isolated after cyanogen bromide cleavage of intact fibrinogen Milano I. This fragment spans from position γ311 to γ336. Amino acid analysis of the abnormal peptide showed the presence of valine and a diminished content of aspartic acid. Sequence analysis demonstrated an amino acid exchange Asp → Val in the γ-chain at position 330.

Original languageEnglish
Pages (from-to)1751-1756
Number of pages6
Issue number6
Publication statusPublished - 1986

ASJC Scopus subject areas

  • Hematology


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