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Hamostaseologie 1994; 14(04): 190-194
DOI: 10.1055/s-0038-1660363
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Schattauer GmbH

Molekularbiologische Grundlagen des Faktor-X-Mangels

H. H. Watzke
1   Abteilung für Hämatologie und Hämostaseologie, Klinik für Innere Medizin I, Wien
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Publication History

Publication Date:
26 June 2018 (online)

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Zusammenfassung

Faktor X ist ein Vitamin-K-abhängiges Plasmaprotein, das eine zentrale Stellung in der Blutgerinnung einnimmt. Durch Interaktionen mit Faktor Vlla/Gewebsfaktor und Faktor IXa/FVIlia wird das Proenzym FXzum Enzym Faktor Xa aktiviert. Faktor Xa wiederum ist das wesentlichste Enzym in der Aktivierung von Prothrombin zu Thrombin. Der hereditäre Faktor-X-Mangel ist eine schwere Erkrankung, die durch eine hämorrhagische Diathese unterschiedlichen Schweregrades gekennzeichnet ist. Durch die Darstellung der Nukleotidsequenz des normalen Faktor-X- . Gens wurde die Aufschlüsselung der genetischen Defekte, die dem hereditären Faktor-X-Mangel zugrunde liegen, ermöglicht. Dies hat nicht zu einer verbesserten Gendiagnostik in den wenigen bisher beschriebenen Fällen geführt, sondern hat vor allem auch Einblicke in die Struktur-Funktions-Beziehungen des Faktor-X- Moleküls erbracht.

Schlüsselwörter

Faktor X - Faktor-X-Mangel - genetische Defekte
 

  • LITERATUR

  • 1 Bernardi F, Marchetti G, Ptracchini P. et al. Partial gene deletion in a family with factor X deficiency. Blood 1989; 73: 2123.
    PubMedGoogle Scholar
  • 2 Bezeaud A, Miyata T, Zheng YZ. et al. Functional consequences of Ser334 to Pro mutation in a factor X variant (Factor X Marseille). Thromb Haemost 1993; 69: 617 (265A).
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Davie EW, Fujikawa K, Kurachi K, Kisiel W. The role of serine proteases in the coagulation cascade. Adv Enzymol 1979; 48: 277.
    PubMedGoogle Scholar
  • 4 Davie EW. The blood coagulation factors: their cDNAs, genes and expression. In: Hemostasis and Thrombosis. Basic Principles and Clinical Practice. Colman RW, Hirsh J, Marder VJ, Salzman EW. (eds). J. B. Lippincott: 1987
    Google Scholar
  • 5 De Grouchy J, Dautzemberg MD, Turleau C. et al. Regional mapping of clotting factors VII and X to 13q34. Expression of factor VII through chromosome 8. Hum Genet 1984; 66: 230.
    PubMedGoogle Scholar
  • 6 Eby CS, Mullane MP, Porche-Sorbet RM, Miletich JP. Characterization of the structure and function of the carboxyterminal peptide of human factor X. Blood 1992; 80 (Suppl 1): 1214A.
    PubMedGoogle Scholar
  • 7 Fukushima Y, Kuroki Y, Iizuka A. Activity and antigen of coagulation factors VII and X in five patients with abnormal chromosome 13. Jpn J Hum Genet 1987; 32: 91.
    CrossrefPubMedGoogle Scholar
  • 8 Fung MR. Molecular genetics of blood coagulation factor X. Dissertation, University of British Columbia, Vancouver, Canada. 1988
    PubMedGoogle Scholar
  • 9 Fung MR, Hay CW, MacGilliray RTA. Characterization of an almost full-length cDNA coding for human blood coagulation factor X. Proc Natl Acad Sci 1985; 82: 3591.
    CrossrefPubMedGoogle Scholar
  • 10 Furie B, Furie BC. The molecular basis of blood coagulation. Cell 1988; 53: 505.
    CrossrefPubMedGoogle Scholar
  • 11 Girolami A, Carli A, Falomo R, De Marco L. Factor X Friuli coagulation disorder. Blut 1973; 17: 151.
    PubMedGoogle Scholar
  • 12 Graham JB, Barrow EM, Hougie C. Stuart clotting defect: II. Genetic aspects of a »new« hemorrhagic state. J Clin Invest 1957; 36: 497.
    PubMedGoogle Scholar
  • 13 Hassan HJ, Guerriero R, Chelucci C. et al. Multiple polymorphic sites in factor X locus. Blood 1988; 71: 1353.
    PubMedGoogle Scholar
  • 14 Hay CW, Robertson KA, Fung MR, Mac Gillivray RTA. RFLPS for Pstl und EcoRI in the human blood clotting factor X gene. Nucl Acids Res 1986; 14: 5118.
    CrossrefPubMedGoogle Scholar
  • 15 Hougie C, Barrow EM, Graham JB. Stuart clotting defect. I. Segregation of an hereditary hemorrhagic state from the heterogeneous group heretofore called »stable factor« (SPCA, proconvertin, factor VII) deficiency. J Clin Invest 1957; 36: 485.
    PubMedGoogle Scholar
  • 16 Huang MN, Hung HL, Stanfield SA, Stanfield SA, High KA. Characterization of the human coagulation factor X promoter. J Biol Chem. 1992. 267 15440.
    Google Scholar
  • 17 Jackson CM, Faktor X. Progress in Hemostasis and Thrombosis 1984. Grune and Stratton. 1984
    PubMedGoogle Scholar
  • 18 Jagadeeswaran P, Reddy SV, Rao KJ. et al. Cloning and characterization of the 5’ end (exon 1) of the gene encoding human factor X. Gene 1989; 84: 517.
    CrossrefPubMedGoogle Scholar
  • 19 James H, Girolami A, Fair DS. Molecular defect in coagulation factor X Friuli’ results from substitution of serine for proline at position 343. Blood 1991; 77: 317.
    PubMedGoogle Scholar
  • 20 James HL, Kumar A. Recapitulation of factor X Friuli by site directed mutagenesis of the recombinant protein. Blood 1992; 80 (Suppl 1): 1216A.
    PubMedGoogle Scholar
  • 21 Jaye R, Ricca G, Kaplan R. et al. Polymorphisms associated with the human factor X (F10) gene. Nucl Acids Res 1985; 22: 8268.
    PubMedGoogle Scholar
  • 22 Kaul RK, Hildebrand B, Roberts S, Jagadeeswaran P. Isolation and characterization of human blood-coagulation factor X cDNA. Gene 1986; 41: 311.
    CrossrefPubMedGoogle Scholar
  • 23 Leytus SP, Chung DW, Kisiel W. et al. Characterization of cDNA coding for human factor X. Proc Natl Acad Sci USA 1984; 82: 3699.
    PubMedGoogle Scholar
  • 24 Leytus SP, Foster DC, Kurachi K, Davie EW. Gene for human factor X: a blood coagulation factor whose gene organization is essentially identical with that of factor IX and protein C. Biochemistry 1986; 25: 5098.
    CrossrefPubMedGoogle Scholar
  • 25 Liles DK, Lefkowitz J, Monroe DM, Roberts HR. Corresponding gamma-car- boxyglutamyl (GLA) residues of factor IX and factor X have different functional consequences. Blood 1992; 80 (Suppl 1): 163a.
    PubMedGoogle Scholar
  • 26 McMullen BA, Fujikawa K, Kisiel W. Complete amino acid sequence of the light chain of human blood coagulation factor X: Evidence for identification of residue 63 as ß-hydroxy aspartic acid. Biochemistry 1983; 22: 2875.
    CrossrefPubMedGoogle Scholar
  • 27 Meissier TL, Wong C, Bovill EG, Factor X. et al. »Stockton«: A missense mutation (GAC to AAC) of the serine protease active site aspartic acid to asparagine. Thromb Haemost 1993; 69: 751 (761A).
    PubMedGoogle Scholar
  • 28 Miao CH, Leytus SP, Chung DW, Davie EW. Liver-specific expression of the gene coding for human factor X, a blood coagulation factor. J Biol Chem 1992; 267: 7395.
    PubMedGoogle Scholar
  • 29 Ott R, Pfeiffer RA. Evidence that activities of coagulation factors VII and X are linked to chromosome 13(q34). Hum Hered 1984; 34: 123.
    CrossrefPubMedGoogle Scholar
  • 30 Pfeiffer RA, Ott R, Gilgenkrantz S, Alexander P. Deficiency of coagulation factors VII and X associated with deletion of a chromosome 13(q34). Evidence from two cases with 46XY, t(23; Y)(qll; q34). Hum Genet 1982; 62: 358.
    PubMedGoogle Scholar
  • 31 Pfeiffer RA, Ott R, Taben KD. Clotting factors VII and X as useful markers of terminal deletion of chromosome 13. Hum Genet 1985; 69: 192.
    CrossrefPubMedGoogle Scholar
  • 32 Racchi M, Watzke HH, High KA, Lively MO. Human coagulation factor X deficiency caused by a mutant signal peptide that blocks cleavage by the signal peptidase but not targeting and translocation to the endoplasmic reticulum. J Biol Chem 1993; 268: 5735.
    PubMedGoogle Scholar
  • 33 Roberts HR, Lozier JN. Other clotting factor deficiencies. In: Hematology. Basic Principles and Practice. Hoffmann R, Benz Jr EJ, Shattil SJ, Furie B, Cohen HJ. (eds). New York: Churchill Livingstone; 1991
    Google Scholar
  • 34 Royle NJ, Fung MR, MacGillivray RTA, Hamerton JL. The gene for clotting factor X is located on chromosome 13q32qter. Cyto- genet Cell Genet 1986; 41: 185.
    PubMedGoogle Scholar
  • 35 Sakamuri VR, Zhou ZQ, Rao KJ. et al. Molecular characterization of human factor X »San Antonio«. Blood 1989; 74: 1486.
    CrossrefPubMedGoogle Scholar
  • 36 Scambler PJ, Williamson R. The structural gene for human coagulation factor X is located on chromosome 13q34. Cytogenet Cell Genet 1985; 39: 231.
    CrossrefPubMedGoogle Scholar
  • 37 Sinha U, Hancock TE, Lin PH. et al. Expression, purification, and characterization of inactive human coagulation factor Xa (Asn322Ala419). Prot Exp Pruif 1992; 03: 518.
    PubMedGoogle Scholar
  • 38 Telfer TP, Denson KW, Wright DR. A »new« coagulation defect. B J Hematol 1956; 02: 308.
    PubMedGoogle Scholar
  • 39 Titani K, Fujikawa K, Enfield D. Bovine FX1 (Stuart factor): Amino acid sequence of the heavy chain. Proc Natl Acad Sci 1975; 72: 3082.
    CrossrefPubMedGoogle Scholar
  • 40 von Heijne G. Signal sequences: the limits of variation. J Mol Biol 1985; 184: 99.
    CrossrefPubMedGoogle Scholar
  • 41 Walter P, Gilmore R, Blobel G. Protein translocation across the endoplasmic reticulum. Cell 1984; 38: 5.
    CrossrefPubMedGoogle Scholar
  • 42 Wallmark A, Larson P, Ljung R. et al. Molecular defect (Gla 26-Asp) and its functional consequences in a hereditary FX deficiency (Factor X »Malmö«). Blood 1991; 78 (Suppl. 1): 229A.
    PubMedGoogle Scholar
  • 43 Wallmark A, Rose VL, Ho C, High KA. A NlalV polymorphism within the human factor X gene. Nucl Acids Res 1993; 19: 4022.
    PubMedGoogle Scholar
  • 44 Watzke HH, Lechner K, Roberts HR. et al. Molecular defect (Gla+ 14-Lys) and ist functional consequences in a hereditary factor X deficiency (Factor X »Vorarlberg«). J Biol Chem 1990; 265: 11982.
    PubMedGoogle Scholar
  • 45 Watzke HH, Wallmark A, Hamagichi N. et al. Factor X »Santo Domingo«. Evidence that the severe clinical phenotype arises from a mutation blocking secretion. J Clin Invest 1991; 88: 1685.
    PubMedGoogle Scholar
  • 46 Watzke HH, Lechner K, Larson P, High KA. Factor X »Vienna«: molecular analysis and in vitro expression of a severe CRM-FX deficiency. Thromb Haemost 1993; 69: 752.
    PubMedGoogle Scholar