Thromb Haemost 1990; 63(02): 231-234
DOI: 10.1055/s-0038-1645200
Original Article
Schattauer GmbH Stuttgart

Antithrombin III Kumamoto: Identification of a Point Mutation and Genotype Analysis of the Family

Hidetsugu Ueyama
1   The First Department of Internal Medicine, Kumamoto University Medical School, Kumamoto, Japan
,
Tatsufumi Murakami
1   The First Department of Internal Medicine, Kumamoto University Medical School, Kumamoto, Japan
2   Department of Biochemistry, Kumamoto University Medical School, Kumamoto, Japan
,
Seiji Nishiguchi
1   The First Department of Internal Medicine, Kumamoto University Medical School, Kumamoto, Japan
2   Department of Biochemistry, Kumamoto University Medical School, Kumamoto, Japan
,
Shuichiro Maeda
2   Department of Biochemistry, Kumamoto University Medical School, Kumamoto, Japan
,
Yoichiro Hashimoto
1   The First Department of Internal Medicine, Kumamoto University Medical School, Kumamoto, Japan
,
Kenji Okajima
3   Department of Laboratory Medicine, Kumamoto University Medical School, Kumamoto, Japan
,
Kazunori Shimada
2   Department of Biochemistry, Kumamoto University Medical School, Kumamoto, Japan
,
Shukuro Araki
1   The First Department of Internal Medicine, Kumamoto University Medical School, Kumamoto, Japan
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 08. August 1989

Accepted after revision 19. Dezember 1989

Publikationsdatum:
24. Juli 2018 (online)

Summary

We previously reported a variant antithrombin III (AT III Kumamoto) associated with a 31-year-old female who suffered from recurrent thrombotic episodes (1). To define the molecular basis for the variant AT III, we used a combination of genomic amplification followed by cloning, sequencing, and hybridization with allele-specific oligonucleotide probes. We obtained evidence for a cytosine to thymine transition in exon 2 (codon 47) of the AT III gene in the proband. This mutation converts arginine 47 to cysteine. Oligonucleotide hybridization procedures were used for confirmation of the mutation and for genotype analysis of the family members

 
  • References

  • 1 Okajima K, Ueyama H, Hashimoto Y, Sasaki Y, Matsumoto K, Okabe H, Inoue M, Araki S, Takatsuki K. Homozygous variant ofantithrombin III that lacks affinity for heparin, AT III Kumamoto. Thromb Haemostas. 1989; 61: 20-24
  • 2 Rosenberg RD, Damus PS. The purification and mechanism of action of human antithrombin-heparin cofactor. J Biol Chem 1973; 248: 6490-6505
  • 3 Björk I, Jackson CM, Jörnvall H, Lavine KK, Nordling K, Salsgiver WJ. The active site of antithrombin: Release of the same proteolyti-cally cleaved form of the inhibitor from complexes with factor IXa, factor Xa and thrombin. J Biol Chem 1982; 257: 2406-2411
  • 4 Blackburn MN, Smith RL, Carson J, Sibley CC. The heparin-binding site of antithrombin III: Identification of a critical tryptophan in the amino acid sequence. J Biol Chem 1984; 259: 939-941
  • 5 Sas G, Blaskó G, Bánhegyi D, Jákó J, Pálos LÁ. Abnormal antithrombinIII (antithrombin III ‘Budapest’) as a cause of a familial thrombophilia. Thromb Diath Haemorrh 1974; 32: 105-115
  • 6 Koide T, Odani S, Takahashi K, Ono T, Sakuragawa N. Antithrombin III Toyama: Replacement of arginine-47 by cysteine in hereditary abnormal antithrombin III that lacks heparin-binding ability. Proc Natl Acad Sci USA 1984; 81: 289-293
  • 7 Duchange N, Chassé JF, Cohen GN, Zakin MM. Molecular characterization of the antithrombinIII Tours deficiency. Thromb Res 1987; 45: 115-121
  • 8 Brunei F, Duchange N, Fischer AM, Cohen GN, Zakin MM. Antithrombin III Alger: A new case of Arg 47→Cys mutation. Am J Hematol 1987; 25: 223-224
  • 9 Chang JY, Tran TH. Antithrombin III Basel: Identification of a Pro-Leu substitution in a hereditary abnormal antithrombin with impaired heparin cofactor activity. J Biol Chem 1986; 261: 1174-1176
  • 10 Owen MC, Borg JY, Soria C, Soria J, Caen J, Carrcll RW. Heparin binding defect in a new antithrombin III variant: Rouen, 47 Argto His. Blood 1987; 69: 1275-1279
  • 11 Bock SC, Wion KL, Vehar GA, Lawn RM. Cloning and expression of the cDNA for human antithrombin III. Nucl Acids Res 1982; 10: 8113-8125
  • 12 Prochownik EV, Markham AF, Orkin SH. Isolation of a cDNA clone for human antithrombin III. J Biol Chem 1983; 258: 8389-8394
  • 13 Chandra T, Stackhouse R, Kidd VJ, Woo SL. Isolation and sequence characterization of a cDNA clone of human antithrombin III. Proc Natl Acad Sci USA 1983; 80: 1845-1848
  • 14 Bock SC, Marrinan JA, Radziejewska E. Antithrombin III Utah: Proline-407 to leucine mutation in a highly conserved region near the inhibitor reactive site. Biochemistry 1988; 27: 6171-6178
  • 15 Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 1988; 239: 487-491
  • 16 Ueyama H, Hashimoto Y, Uchino M, Sasaki Y, Uyama E, Okajima K, Araki S. Progressing ischemic stroke in a homozygote with variant antithrombin III. Stroke 1989; 20: 815-818
  • 17 Kunkel LM, Smith KD, Boyer SH, Borgaonkar DS, Wachtel SS, Miller OJ, Breg WR, Jones HW, Rary JM. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci USA 1977; 74: 1245-1249
  • 18 Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain terminating inhibitions. Proc Natl Acad Sci USA 1977; 74: 5463-5467
  • 19 Thein SL, Wallace RB. The use of synthetic oligonucleotides as specific hybridization probes in the diagnosis of genetic disorders. In: Davies KE. (ed.) Human Genetic Diseases, a Practical Approach. Oxford, Washington, Dc: IRL Press; 1986: 33-50
  • 20 Nagy I, Losonczy H, Szaksz I, Temesi C, Hergert K. An analysis of clinical and laboratory data in patients with congenital antithrombin III (AT-III)deficiency. Acta Med Acad Sci Hung 1979; 36: 53-60
  • 21 Penner JA, Hassouna H, Hunter MJ, Chockley M. A clinically silent antithrombin III defect inan Ann Arbor family. Thromb Haemostas 1979; 42: 186
  • 22 Wolf M, Boyer C, Lavergne JM, Larrieu MJ. A new familial variant of antithrombin III: “Antithrombin III Paris”. Br J Haematol 1982; 51: 285-295
  • 23 Fischer AM, Gazengel C, Dautzenberg MD, Benhammo J, Béguin S, Vergoz D. A new case of abnormal antithrombin III (AT III): biological characteristics and thromboembolic accidents management. Thromb Haemostas 1983; 50: 358
  • 24 Sakuragawa N, Takahashi K, Kondo S, Koide T. Antithrombin III Toyama: A hereditary abnormalantithrombin III of a patient with recurrent thrombophlebitis. Thromb Res 1983; 31: 305-317
  • 25 Girolami A, Pengo V, Patrassi GM, Cappellato G, Vianello C, Cartei L. Antithrombin III Padua: A “new” congenital antithrombin III abnormality with normal or near normal activity, normal antigen, abnormal migration and no thrombotic disease. Folia Haematol 1983; 110: 98-111
  • 26 Girolami A, Fabris F, Capellato G, Sainati L, Boeri G. Antithrombin III (AT III) Padua2: A “new” congenital abnormality with defective heparin co-factor activities but no thrombotic disease. Blut 1983; 47: 93-103
  • 27 Chasse JF, Esnard F, Guitton JD, Mouray H, Perigois F, Faucon-neau G, Gauthier F. An abnormal plasma antithrombin with no apparent affinity for heparin. Thromb Res 1984; 34: 297-302
  • 28 Fischer AM, Cornu P, Sternberg C, Mériane F, Dautzenberg MD, Chafa O, Beguin S, Desnos M. Antithrombin III Alger: A new homozygous AT III variant. Thromb Haemostas 1986; 55: 218-221
  • 29 Boyer C, Wolf M, Vedrenne J, Meyer D, Larrieu MJ. Homozygous variant ofantithrombin III: AT III Fontainebleau. Thromb Haemos tas 1986; 56: 18-22
  • 30 Borg JY, Owen MC, Soria C, Soria J, Caen J, Carrell RW. Proposed heparin binding site in antithrombin based on arginine 47. A new vaiiant Rouen-II, 47 Aig to Sei. J Clin Invest 1988; 81: 1292-1296
  • 31 de Moerloose PA, Reber G, , Vernet Ph, Minazio Ph, Bouvier CA. Antithrombin III Geneva: A hereditary abnormal AT III with defective heparin cofactor activity. Thromb Haemostas 1987; 57: 154-157
  • 32 Roussel B, Dieval J, Gross S, Claisse JF, Delobel J. A new asymptomatic type III variant of antithrombin III with decrease heparin cofactor activity: AT III Amiens. Thromb Haemostas 1987; 58: 427
  • 33 Barker D, Schafer M, White R. Restriction sites containing CpG show a higher frequency of polymorphism in human DNA. Cell 1984; 36: 131-138
  • 34 Youssoufian H, Kazazian HH, Phillips DG, Aronis S, Tsiftis G, Brown VA, Antonarakis SE. Recurrent mutations in haemophilia A give evidence for CpG mutation hotspots. Nature 1986; 324: 380-382
  • 35 Coulondre C, Miller JH, Farabaugh PJ, Gilbert W. Molecular basis of base substitution hotspots in Escherichia coli. Nature 1978; 274: 775-780
  • 36 Molho-Sabatier P, Aiach M, Gaillard I, Fiessinger JN, Chadeuf G, Clauser E. Characterization of seven AT III variants using gene amplification. Identification of a new point mutation 384 Ala→Pro in a reactive site variant. Thromb Haemostas 1989; 62: 480
  • 37 Thein SL, Lane DA. Use of synthetic oligonucleotides in the characterization of antithrombin III Northwick Park (393 CGT→TGT) and antithrombin III Glasgow (393 CGT→CAT). Blood 1988; 72: 1817-1821