Print Email Facebook Twitter Molecular basis for fibrinogen Dusart (Aα 554 Arg → Cys) and its association with abnormal fibrin polymerization and thrombophilia Title Molecular basis for fibrinogen Dusart (Aα 554 Arg → Cys) and its association with abnormal fibrin polymerization and thrombophilia Author Koopman, J. Haverkate, F. Grimbergen, J. Lord, S.T. Mosesson, M.W. DiOrio, J.P. Siebenlist, K.S. Legrand, C. Soria, J. Soria, C. Caen, J.P. Instituut voor verouderings- en vaatziekten onderzoek TNO Publication year 1993 Abstract The molecular defect in the abnormal fibrinogen Dusart (Paris V) that is associated with thrombophilia was determined by sequence analysis of genomic DNA that had been amplified using the polymerase chain reaction. The propositus was heterozygous for a single base change (C → T) in the Aα- chain gene, resulting in the amino acid substitution Aα 554 Arg → Cys. Restriction analysis of the amplified DNA derived from the family members showed that his father and his two sons were also heterozygous. Electron microscopic studies on fibrin formed from purified fibrinogen Dusart demonstrated fibers that were much thinner than in normal fibrin. In contrast to the previously observed defective binding of plasminogen, the binding of thrombospondin to immobilized fibrinogen Dusart was similar to that of normal fibrinogen. Immunoblot analysis of plasma fibrinogen demonstrated that a substantial part of the fibrinogen Dusart molecules were disulfide-linked to albumin. The plasma of the affected family members also contained fibrinogen- albumin complexes. Furthermore, small amounts of high molecular weight complexes containing fibrinogen were detected in all the heterozygous individuals. These data indicate that the molecular abnormality in fibrinogen Dusart (Aα 554 Arg → Cys) results in defective lateral association of the fibrin fibers and disulfide-linked complex formation with albumin, and is associated with a family history of recurrent thrombosis in the affected individuals. Chemicals/CAS: antithrombin III, 90170-80-2; fibrinogen, 9001-32-5; plasminogen, 9001-91-6; protein C, 60202-16-6; thrombin, 9002-04-4; Fibrin, 9001-31-4; fibrinogen Dusard; Fibrinogen, 9001-32-5; Fibrinogens, Abnormal; Platelet Membrane Glycoproteins; Sulfhydryl Compounds; Thrombospondins Subject HealthAα chainalbumin, disulfide-linkeddysfibrogenemiagene analysisalbuminantithrombin iiifibrinogenplasminogenprotein cprotein sthrombinamino acid substitutionblood clottingcomplex formationcontrolled studydisulfide bonddna sequencedysfibrinogenemiafemalefibrin polymerizationgene amplificationgenetic analysisheterozygotenucleic acid base substitutionpolymerase chain reactionpriority journalthrombosisAdultBase SequenceBlood Coagulation DisordersCase ReportFibrinFibrinogenFibrinogens, AbnormalGene AmplificationHumanImmunoblottingMaleMicroscopy, ElectronMolecular Sequence DataMutationPlatelet Membrane GlycoproteinsProtein BindingSequence Analysis, DNAStructure-Activity RelationshipSulfhydryl CompoundsSupport, Non-U.S. Gov'tSupport, U.S. Gov't, P.H.S.ThrombosisThrombospondins To reference this document use: http://resolver.tudelft.nl/uuid:a3b8666c-b984-4bc1-93de-02b10de684b9 TNO identifier 232204 ISSN 0021-9738 Source Journal of Clinical Investigation, 91 (4), 1637-1643 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.