Download PDF
Thromb Haemost 1992; 68(05): 534-538
DOI: 10.1055/s-0038-1646313
Original Article
Schattauer GmbH Stuttgart

Heterozygous Abnormal Fibrinogen Osaka III with the Replacement of γ Arginine-275 by Histidine Has an Apparently Higher Molecular Weight γ-Chain Variant

Nobuhiko Yoshida
1   The institute of Hematology, Jichi Medical School, Tochigi, Japan
2   The Department of Internal Medicine, Toshiba General Hospital, Tokyo, Japan
,
Shingi Imaoka
3   The Department of Surgery, the Center for Adult Diseases-Osaka, Osaka, Japan
,
Hajime Hirata
4   The Department of Life Science, Faculty of Science, Himeji Institute of Technology, Hyogo, Japan
,
Michio Matsuda
1   The institute of Hematology, Jichi Medical School, Tochigi, Japan
,
Shinji Asakura
1   The institute of Hematology, Jichi Medical School, Tochigi, Japan
› Author Affiliations
Further Information

Publication History

Received 04 March 1992

Accepted after revision 22 June 1992

Publication Date:
04 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Congenitally abnormal fibrinogen Osaka III with the replacement of γ Arg-275 by His was found in a 38-year-old female with no bleeding or thrombotic tendency. Release of fibrinopeptide(s) by thrombin or reptilase was normal, but her thrombin or reptilase time in the absence of calcium was markedly prolonged and the polymerization of preformed fibrin monomer which was prepared by the treatment of fibrinogen with thrombin or reptilase was also markedly defective. Propositus' fibrinogen had normal crosslinking abilities of α- and γ-chains. Analysis of fibrinogen chains on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the system of Laemmli only revealed the presence of abnormal γ-chain with an apparently higher molecular weight, the presence of which was more clearly detected with SDS-PAGE of fibrin monomer obtained by thrombin treatment. Purified fragment D1 of fibrinogen Osaka III also seemed to contain an apparently higher molecular weight fragment D1 γ remnant on Laemmli gels, which was digested faster than the normal control by plasmin in the presence of [ethy-lenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA).

 

  • REFERENCES

  • 1 Kehl M, Henschen A, Tavori S, Rimon A, Soria J, Soria C. The structural error in fibrinogen Haifa, a genetically abnormal fibrinogen with a polymerization defect. Proceedings of the 8th International Congress on Thrombosis, Istanbul 1984 p 82 (abstr)
    PubMedGoogle Scholar
  • 2 Reber P, Furl an M, Rupp C, Kehl M, Henschen A, Mannucci PM, Beck EA. Characterization of fibrinogen Milano I: Amino acid exchange γ 330 Asp → Val impairs fibrin polymerization. Blood 1986; 67: 1751-1756
    PubMedGoogle Scholar
  • 3 Reber P, Furlan M, Henschen A, Kaudewitz H, Barbui T, Hilgard P, Nenci GG, Berrettini M, Beck EA. Three abnormal fibrinogen variants with the same amino acid substitution (γ 275 Arg → His): Fibrinogens Bergamo II, Essen and Perugia. Thromb Haemostas 1986; 56: 401-406
    PubMedGoogle Scholar
  • 4 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227: 680-685
    PubMedGoogle Scholar
  • 5 Yoshida N, Okuma M, Moroi M, Matsuda M. A lower molecular weight γ-chain variant in a congenital abnormal fibrinogen (Kyoto). Blood 1986; 68: 703-707
    PubMedGoogle Scholar
  • 6 Yoshida N, Ota K, Moroi M, Matsuda M. An apparently higher molecular weight γ-chain variant in a new congenital abnormal fibrinogen Tochigi characterized by the replacement of γ arginine-275 by cysteine. Blood 1988; 71: 480-487
    PubMedGoogle Scholar
  • 7 Yoshida N, Terukina S, Okuma M, Moroi M, Aoki N, Matsuda M. Characterization of an apparently lower molecular weight γ-chain variant in fibrinogen Kyoto I. The replacement of γ-asparagine 308 by lysine which causes accelerated cleavage of fragment D1 by plasmin and the generation of a new plasmin cleavage site. J Biol Chem. 1988; 263: 13848-13856
    PubMedGoogle Scholar
  • 8 Terukina S, Matsuda M, Hirata H, Takeda Y, Miyata T, Takao T, Shimonishi Y. Substitution of γ Arg-275 by Cys in an abnormal fibrinogen, “fibrinogen Osaka II”. Evidence for a unique solitary cystine structure at the mutation site. J Biol Chem 1988; 263: 13579-13587
    PubMedGoogle Scholar
  • 9 Miyata T, Furukawa K, Iwanaga S, Takamatsu J, Saito H. Fibrinogen Nagoya, a replacement of glutamine-329 by arginine in the γ-chain that impairs the polymerization of fibrin monomer. J Biochem (Tokyo) 1989; 105: 10-14
    CrossrefPubMedGoogle Scholar
  • 10 Schmelzer CH, Ebert RF, Bell WR. Fibrinogen Baltimore IV: Congenital dysfibrinogenemia with a γ 275 (Arg → Cys) substitution. Thromb Res 1989; 56: 307-316
    CrossrefPubMedGoogle Scholar
  • 11 Terukina S, Yamazumi K, Okamoto K, Yamashita H, Ito Y, Matsuda M. Fibrinogen Kyoto III: A congenital dysfibrinogen with a γ aspartic acid-330 to tyrosine substitution manifesting impaired fibrin monomer polymerization. Blood 1989; 74: 2681-2687
    PubMedGoogle Scholar
  • 12 Bantia S, Bell WR, Dang CV. Polymerization defect of fibrinogen Baltimore III due to a γ Asn308 → He mutation. Blood. 1990; 75: 1659-1663
    PubMedGoogle Scholar
  • 13 Koopman J, Haverkate F, Briët E, Lord ST. A congenitally abnormal fibrinogen (Vlissingen) with a 6-base deletion in the γ-chain gene, causing defective calcium binding and impaired fibrin polymerization. J Biol Chem 1991; 266: 13456-13461
    PubMedGoogle Scholar
  • 14 Yamazumi K, Terukina S, Onohara S, Matsuda M. Normal plasmic cleavage of the γ-chain variant of “fibrinogen Saga” with an Arg-275 to His substitution. Thromb Haemostas 1988; 60: 476-480
    PubMedGoogle Scholar
  • 15 Gralnick HR, Givelber HM, Shainoff JR, Finlayson JS. Fibrinogen Bethesda: A congenital dysfibrinogenemia with delayed fibrinopeptide release. J Clin Invest 1971; 50: 1819-1830
    CrossrefPubMedGoogle Scholar
  • 16 Doolittle RF, Cassman KG, Cottrell BA, Friezner SJ, Hucko JT, Takagi T. Amino acid sequence studies on the α chain of human fibrinogen. Characterization of 11 cyanogen bromide fragments. Biochemistry 1977; 16: 1703-1709
    CrossrefPubMedGoogle Scholar
  • 17 Kehl M, Lottspeich F, Henschen A. High-performance liquid chromatography of proteins as applied to fibrinogen chains. Hoppe-Seyler's Z Physiol Chem 1982; 363: 1501-1505
    PubMedGoogle Scholar
  • 18 Aoki N, Moroi M, Sakata Y, Yoshida N, Matsuda M. Abnormal plasminogen, a hereditary molecular abnormality found in a patient with recurrent thrombosis. J Clin Invest 1978; 61: 1186-1195
    CrossrefPubMedGoogle Scholar
  • 19 Yoshida N, Weksler B, Nachman R. Purification of human platelet calcium-activated protease. Effect on platelet and endothelial function. J Biol Chem 1982; 258: 7168-7174
    PubMedGoogle Scholar
  • 20 Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Proc Natl Acad Sci USA 1979; 76: 4350-4354
    CrossrefPubMedGoogle Scholar
  • 21 Burnette WN. “Western blotting”: Electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem 1981; 112: 195-203
    CrossrefPubMedGoogle Scholar
  • 22 Yoshida N, Hirata H, Morigami Y, Imaoka S, Matsuda M, Yamazumi K, Asakura S. Characterization of an abnormal fibrinogen Osaka V with the replacement of γ arginine 375 by glycine. The lack of high affinity calcium binding to D-domains and the lack of protective effect of calcium on fibrinolysis. J Biol Chem 1992; 267: 2753-2759
    PubMedGoogle Scholar
  • 23 Soria J, Soria C, Samama M, Tabori S, Kehl M, Henschen A, Nieuwenhuizen W, Rimon A, Tatarski I. Fibrinogen Haifa: Fibrinogen variant with absence of protective effect of calcium on plasmin degradation of gamma chains. Thromb Haemostas 1987; 57: 310-313
    PubMedGoogle Scholar
  • 24 Yamazumi K, Shimura K, Terukina S, Takahashi N, Matsuda M. A γ methionine-310 to threonine substitution and consequent N-glycosyla-tion at γ asparagine-308 identified in a congenital dysfibrinogenemia associated with posttraumatic bleeding, fibrinogen Asahi. J Clin Invest 1989; 83: 1590-1597
    CrossrefPubMedGoogle Scholar
  • 25 Budzynski AZ, Marder VJ, Ménaché D, Guillin M-C. Defect in the gamma polypeptide chain of a congenital abnormal fibrinogen (Paris I). Nature 1974; 252: 66-68
    CrossrefPubMedGoogle Scholar
  • 26 Brosstad F, Teige B, Olaisen B, Gravem K, Godal HC, Stormorken H. Two-dimensional electrophoretic characterization (ISO-DALT) of fibrinogen and fibrin subunit chains from four different genetic dysfibrinogen variants. In: Fibrinogen - Structure, Functional Aspects, Metabolism, Vol 2. Haverkate F, Henschen A, Nieuwenhuizen W, Straub PW. (eds) Walter de Gruyter, Berlin: 1983. pp 145-153
    Google Scholar
  • 27 Polack B, Valiron O, Concord E, Freyssinet JM, Hudry-Clergeon G. Molecular characterization of an abnormal fibrinogen by two-dimensional electrophoresis. Clin Chem 1984; 30: 2093-2097
    PubMedGoogle Scholar
  • 28 Rupp C, Kuyas C, Häberli A, Furlan M, Perret BA, Beck EA. Fibrinogen Bern I: A hereditary fibrinogen variant with defective conformational stabilization by calcium ions. In: Fibrinogen - Recent Biochemical and Medical Aspects. Henschen A, Graeff H, Lottspeich F. (eds) Walter de Gruyter, Berlin: 1982. pp 167-181
    Google Scholar
  • 29 Bantia S, Mane SM, Bell WR, Dang CV. Fibrinogen Baltimore I: Polymerization defect associated with a γ 292Gly → Val (GGC → GTC) mutation. Blood. 1990; 76: 2279-2283
    PubMedGoogle Scholar
  • 30 Siebenlist KR, Mosesson MW, DiOrio JP, Tavori S, Tatarsky I, Rimon A. The polymerization of fibrin prepared from fibrinogen Haifa (γ 275Arg → His). Thromb Haemostas. 1989; 62: 875-879
    PubMedGoogle Scholar
  • 31 Yoshida N, Okuma M, Hirata H, Matsuda M, Yamazumi K, Asakura S. Fibrinogen Kyoto II, a new congenitally abnormal molecule, characterized by the replacement of Aα proline-18 by leucine. Blood 1991; 78: 149-153
    PubMedGoogle Scholar