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Hamostaseologie 2002; 22(02): 76-81
DOI: 10.1055/s-0037-1619535
Übersichtsarbeit
Schattauer GmbH

Molekulare Varianten des Fibrinogens

Molecular variants of fibrinogen
H. Plendl
1   Institut für Humangenetik im Universitätsklinikum Kiel (Direktor: Prof. Dr. med. W. Grote), Deutschland
,
A. Caliebe
1   Institut für Humangenetik im Universitätsklinikum Kiel (Direktor: Prof. Dr. med. W. Grote), Deutschland
,
W. Grote
1   Institut für Humangenetik im Universitätsklinikum Kiel (Direktor: Prof. Dr. med. W. Grote), Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
27 December 2017 (online)

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Zusammenfassung

Im letzten Schritt der Blutgerinnung lagern sich Fibrinmonomere aneinander und werden durch Faktor XIIIa kovalent verbunden. Mutationen in einem der drei Gene, die für die Fibrinogenpeptide kodieren, können diesen Prozess stören und zu Afibrinogenämie oder Dysfibrinogenämie führen. Sie können sogar Ursache der hereditären renalen Amyloidose sein. In dieser kurzen Übersicht beschreiben wir einige molekulare Aspekte dieser Erkrankungen.

Summary

In the final step of blood coagulation, fibrin monomers polymerize spontaneously and are covalently linked by factor XIIIa. Mutations in one of the three genes coding for the fibrinogen peptides may disturb this process and lead to diseases such as afibrinogenemia or dysfibrinogenemia, or may even cause hereditary renal amyloidosis. In the brief overview presented here we summarize some of the molecular aspects of these diseases.

Schlüsselwörter

Dysfibrinogenämie - Afibrinogenämie - renale Amyloidose - Molekulargenetik - Mutation

Keywords

Dysfibrinogenemia - afibrinogenemia - renal amyloidosis - molecular genetics - mutation
 

  • Literatur

  • 1 Asselta R, Duga S, Spena S. et al. Congenital afibrinogenemia: mutations leading to premature termination codons in fibrinogen A alphachain gene are not associated with the decay of the mutant mRNAs. Blood 2001; 98: 3685-92.
    CrossrefPubMedGoogle Scholar
  • 2 Benson MD, Liepnieks J, Uemichi T. et al. Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain. Nat Genet 1993; 3: 252-5.
    CrossrefPubMedGoogle Scholar
  • 3 Blake GJ, Schmitz C, Lindpaintner K. et al. Mutation in the promoter region of the betafibrinogen gene and the risk of future myocardial infarction, stroke and venous thrombosis. Eur Heart J 2001; 22: 2262-6.
    CrossrefPubMedGoogle Scholar
  • 4 Booth DR, Tan SY, Booth SE. et al. Hereditary hepatic and systemic amyloidosis caused by a new deletion/insertion mutation in the apolipoprotein AI gene. J Clin Invest 1996; 97: 2714-21.
    CrossrefPubMedGoogle Scholar
  • 5 Brennan SO, Fellowes AP, Faed JM. et al. Hypofibrinogenemia in an individual with 2 coding (gamma82 A→G and Bbeta235 P→L) and 2 noncoding mutations. Blood 2000; 95: 1709-13.
    PubMedGoogle Scholar
  • 6 Brennan SO, Fellowes AP, George PM. Molecular mechanisms of hypo- and afibrinogenemia. Ann N Y Acad Sci 2001; 936: 91-100.
    PubMedGoogle Scholar
  • 7 Brennan SO, Wyatt JM, Fellowes AP. et al. Gamma371 Thr→Ile substitution in the fibrinogen gammaD domain causes hypofibrinogenaemia. Biochim Biophys Acta 2001; 1550: 183-8.
    CrossrefPubMedGoogle Scholar
  • 8 Brennan SO, Wyatt JM, May S. et al. Hypofibrinogenemia due to novel 316 Asp→Tyr substitution in the fibrinogen Bbeta chain. Thromb Haemost 2001; 85: 450-3.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Brown ET, Fuller GM. Detection of a complex that associates with the Bbeta fibrinogen G-455-A polymorphism. Blood 1998; 92: 3286-93.
    PubMedGoogle Scholar
  • 10 Carter AM, Catto AJ, Grant PJ. Association of the alpha-fibrinogen Thr312Ala polymorphism with poststroke mortality in subjects with atrial fibrillation. Circulation 1999; 99: 2423-6.
    CrossrefPubMedGoogle Scholar
  • 11 Côté HC, Lord ST, Pratt KP. gamma-Chain dysfibrinogenemias: molecular structure-function relationships of naturally occurring mutations in the gamma chain of human fibrinogen. Blood 1998; 92: 2195-212.
    PubMedGoogle Scholar
  • 12 Credo RB, Curtis CG, Lorand L. Alpha-chain domain of fibrinogen controls generation of fibrinoligase (coagulation factor XIIIa). Calcium ion regulatory aspects. Biochemistry 1981; 20: 3770-8.
    CrossrefPubMedGoogle Scholar
  • 13 Doolittle RF, Spraggon G, Everse SJ. Crystal structures of fragments D and double-D from fibrinogen and fibrin. Thromb Haemost 1999; 82: 271-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Duga S, Asselta R, Santagostino E. et al. Missense mutations in the human beta fibrinogen gene cause congenital afibrinogenemia by impairing fibrinogen secretion. Blood 2000; 95: 1336-41.
    PubMedGoogle Scholar
  • 15 Everse SJ, Spraggon G, Doolittle RF. A three-dimensional consideration of variant human fibrinogens. Thromb Haemost 1998; 80: 1-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Fellowes AP, Brennan SO, George PM. Identification and characterization of five new fibrinogen gene polymorphisms. Ann N Y Acad Sci 2001; 936: 536-41.
    PubMedGoogle Scholar
  • 17 Fowler WE, Erickson HP. Trinodular structure of fibrinogen. Confirmation by both shadowing and negative stain electron microscopy. J Mol Biol 1979; 134: 241-9.
    CrossrefPubMedGoogle Scholar
  • 18 Gerdes S, Plendl H, Zunker P. et al. Fibrinogen Kiel III:A novel gamma-chain A108G substitution in two unrelated patients with acute ischaemic stroke. Ann Hematol 2002; 81 (Suppl. 01) A21.
    PubMedGoogle Scholar
  • 19 Gillmore JD, Booth DR, Rela M. et al. Curative hepatorenal transplantation in systemic amyloidosis caused by the Glu526Val fibrinogen alpha-chain variant in an English family. QJM 2000; 93: 269-75.
    CrossrefPubMedGoogle Scholar
  • 20 Hamidi Asl L, Liepnieks JJ, Uemichi T. et al. Renal amyloidosis with a frame shift mutation in fibrinogen aalpha-chain gene producing a novel amyloid protein. Blood 1997; 90: 4799-805.
    PubMedGoogle Scholar
  • 21 Haverkate F, Samama M. Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC Subcommittee on Fibrinogen. Thromb Haemost 1995; 73: 151-61.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Hogan KA, Lord ST, Okumura N. et al. A functional assay suggests that heterodimers exist in two C-terminal gamma-chain dysfibrinogens: Matsumoto I and Vlissingen/Frankfurt IV. Thromb Haemost 2000; 83: 592-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Homer VM, Brennan SO, George PM. Four novel polymorphisms in the fibrinogen Aalpha gene. Thromb Haemost 2002; 87: 354-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Koopman J, Haverkate F. Hereditary variants of human fibrinogens. In: Bloom AL, Forbes CD, Thomas PD. et al. (ed). Haemostasis and thrombosis. Edinburgh: Churchill Livingstone; 1994: 515-29
    Google Scholar
  • 25 Lane DA, Grant PJ. Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease. Blood 2000; 95: 1517-32.
    PubMedGoogle Scholar
  • 26 Lehmann W. Krankheiten der Blutgerinnung. In: Becker PE. (ed). Humangenetik. Band III/3: Hämatologie. Stuttgart: Georg Thieme Verlag; 1976: 344-51.
    Google Scholar
  • 27 Lounes KC, Soria C, Mirshahi SS. et al. Fibrinogen Ales: a homozygous case of dysfibrinogenemia (gamma-Asp(330)→Val) characterized by a defective fibrin polymerization site “a”. Blood 2000; 96: 3473-9.
    PubMedGoogle Scholar
  • 28 Matsuda M, Sugo T, Yoshida N. et al. Structure and function of fibrinogen: insights from dysfibrinogens. Thromb Haemost 1999; 82: 283-90.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Meh DA, Mosesson MW, Siebenlist KR. et al. Fibrinogen Naples I (B beta A68T) nonsubstrate thrombin-binding capacities. Thromb Res 2001; 103: 63-73.
    CrossrefPubMedGoogle Scholar
  • 30 Mimuro J, Kawata Y, Niwa K. et al. A new type of Ser substitution for gamma Arg-275 in fibrinogen Kamogawa I characterized by impaired fibrin assembly. Thromb Haemost 1999; 81: 940-4.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Miyata T, Terukina S, Matsuda M. et al. Fibrinogens Kawaguchi and Osaka: an amino acid substitution of A alpha arginine-16 to cysteine which forms an extra interchain disulfide bridge between the two A alpha chains. J Biochem (Tokyo) 1987; 102: 93-101.
    CrossrefPubMedGoogle Scholar
  • 32 Morsdorf S, Jung F, Seyfert UT. et al. Haemostatical and rheological aspects of dysfibrinogenemia. Clin Hemorheol Microcirc 1997; 17: 13-9.
    PubMedGoogle Scholar
  • 33 Neerman-Arbez M, Honsberger A, Antonarakis SE. et al. Deletion of the fibrinogen alpha-chain gene (FGA) causes congenital afibrogenemia. J Clin Invest 1999; 103: 215-8.
    CrossrefPubMedGoogle Scholar
  • 34 Neerman-Arbez M. The molecular basis of inherited afibrinogenaemia. Thromb Haemost 2001; 86: 154-63.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Nguyen F, Drouet L, Boisseau M. et al. Erythrocyte hyperaggregation and thrombogenic dysfibrinogenemia. Clin Hemorheol Microcirc 1998; 18: 235-43.
    PubMedGoogle Scholar
  • 36 Pepys MB, Hawkins PN, Booth DR. et al. Human lysozyme gene mutations cause hereditary systemic amyloidosis. Nature 1993; 362: 553-7.
    CrossrefPubMedGoogle Scholar
  • 37 Peyvandi F, Mannucci PM. Rare coagulation disorders. Thromb Haemost 1999; 82: 1207-14.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 Plendl H, Padeken M, Caliebe A. et al. Thrombotic events and recurrent miscarriages in a family with dysfibrinogenemia. Ann Hematol 2000; 79 (Suppl. 01) A94.
    PubMedGoogle Scholar
  • 39 Remijn JA, Lounes KC, Hogan KA. et al. Mutations on fibrinogen (gamma 316-322) are associated with reduction in platelet adhesion under flow conditions. Ann N Y Acad Sci 2001; 936: 444-8.
    PubMedGoogle Scholar
  • 40 Seydewitz HH, Gram J, Bruhn HD. et al. Fibrinogen Kiel: a congenital dysfibrinogenaemia with (A alpha-16 Arg→His) substitution characterized by HPLC without prior isolation of fibrinogen. Blood Coagul Fibrinolysis 1991; 2: 501-6.
    CrossrefPubMedGoogle Scholar
  • 41 Spraggon G, Everse SJ, Doolittle RF. Crystal structures of fragment D from human fibrinogen and its crosslinked counterpart from fibrin. Nature 1997; 389: 455-62.
    CrossrefPubMedGoogle Scholar
  • 42 Sugo T, Nakamikawa C, Yoshida N. et al. Endlinked homodimers in fibrinogen Osaka VI with a B beta-chain extension lead to fragile clot structure. Blood 2000; 96: 3779-85.
    PubMedGoogle Scholar
  • 43 Terasawa F, Okumura N, Higuchi Y. et al. Fibrinogen Matsumoto III: a variant with gamma275 Arg→Cys (CGC→TGC) – comparison of fibrin polymerization properties with those of Matsumoto I (gamma364 Asp→His) and Matsumoto II (gamma308 Asn→Lys). Thromb Haemost 1999; 81: 763-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 44 Terasawa F, Okumura N, Kitano K. et al. Hypofibrinogenemia associated with a heterozygous missense mutation gamma153Cys to arg (Matsumoto IV): in vitro expression demonstrates defective secretion of the variant fibrinogen. Blood 1999; 94: 4122-31.
    PubMedGoogle Scholar
  • 45 Tuddenham EGD, Cooper DN. The molecular genetics of haemostasis and its inherited disorders. Oxford, New York, Tokyo: Oxford University Press; 1994: 248-70.
    Google Scholar
  • 46 Uemichi T, Liepnieks JJ, Alexander F. et al. The molecular basis of renal amyloidosis in Irish-American and Polish-Canadian kindreds. Q J M 1996; 89: 745-50.
    CrossrefPubMedGoogle Scholar
  • 47 Uemichi T, Liepnieks JJ, Benson MD. Hereditary renal amyloidosis with a novel variant fibrinogen. J Clin Invest 1994; 93: 731-6.
    CrossrefPubMedGoogle Scholar
  • 48 Uemichi T, Liepnieks JJ, Yamada T. et al. A frame shift mutation in the fibrinogen A alpha chain gene in a kindred with renal amyloidosis. Blood 1996; 87: 4197-203.
    PubMedGoogle Scholar
  • 49 Weisel JW, Veklich Y, Collet JP. et al. Structural studies of fibrinolysis by electron and light microscopy. Thromb Haemost 1999; 82: 277-82.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 50 Witt I. Biochemie der Blutgerinnung und Fibrinolyse. Weinheim: Verlag Chemie; 1975: 32-45.
    Google Scholar
  • 51 Yu S, Sher B, Kudryk B. et al. Fibrinogen precursors. Order of assembly of fibrinogen chains. J Biol Chem 1984; 259: 10574-81.
    PubMedGoogle Scholar