Molekularbiologische Grundlagen des Faktor-X-Mangels

H. H. Watzke

doi:10.1055/s-0038-1660363

Hämostaseologie, Table of Contents

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

Übersichtsarbeiten/Review Articles

Schattauer GmbH

Molekularbiologische Grundlagen des Faktor-X-Mangels

H. H. Watzke

¹Abteilung für Hämatologie und Hämostaseologie, Klinik für Innere Medizin I, Wien

› Author Affiliations

Abstract

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

Full Text

References

LITERATUR
1 Bernardi F, Marchetti G, Ptracchini P. et al. Partial gene deletion in a family with factor X deficiency. Blood 1989; 73: 2123.
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).
3 Davie EW, Fujikawa K, Kurachi K, Kisiel W. The role of serine proteases in the coagulation cascade. Adv Enzymol 1979; 48: 277.
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
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.
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.
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.
8 Fung MR. Molecular genetics of blood coagulation factor X. Dissertation, University of British Columbia, Vancouver, Canada. 1988
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.
10 Furie B, Furie BC. The molecular basis of blood coagulation. Cell 1988; 53: 505.
11 Girolami A, Carli A, Falomo R, De Marco L. Factor X Friuli coagulation disorder. Blut 1973; 17: 151.
12 Graham JB, Barrow EM, Hougie C. Stuart clotting defect: II. Genetic aspects of a »new« hemorrhagic state. J Clin Invest 1957; 36: 497.
13 Hassan HJ, Guerriero R, Chelucci C. et al. Multiple polymorphic sites in factor X locus. Blood 1988; 71: 1353.
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.
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.
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.
17 Jackson CM, Faktor X. Progress in Hemostasis and Thrombosis 1984. Grune and Stratton. 1984
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.
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.
20 James HL, Kumar A. Recapitulation of factor X Friuli by site directed mutagenesis of the recombinant protein. Blood 1992; 80 (Suppl 1): 1216A.
21 Jaye R, Ricca G, Kaplan R. et al. Polymorphisms associated with the human factor X (F10) gene. Nucl Acids Res 1985; 22: 8268.
22 Kaul RK, Hildebrand B, Roberts S, Jagadeeswaran P. Isolation and characterization of human blood-coagulation factor X cDNA. Gene 1986; 41: 311.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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
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.
35 Sakamuri VR, Zhou ZQ, Rao KJ. et al. Molecular characterization of human factor X »San Antonio«. Blood 1989; 74: 1486.
36 Scambler PJ, Williamson R. The structural gene for human coagulation factor X is located on chromosome 13q34. Cytogenet Cell Genet 1985; 39: 231.
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.
38 Telfer TP, Denson KW, Wright DR. A »new« coagulation defect. B J Hematol 1956; 02: 308.
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.
40 von Heijne G. Signal sequences: the limits of variation. J Mol Biol 1985; 184: 99.
41 Walter P, Gilmore R, Blobel G. Protein translocation across the endoplasmic reticulum. Cell 1984; 38: 5.
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.
43 Wallmark A, Rose VL, Ho C, High KA. A NlalV polymorphism within the human factor X gene. Nucl Acids Res 1993; 19: 4022.
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.
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.
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.