Thromb Haemost 1995; 74(03): 822-827
DOI: 10.1055/s-0038-1649830
Original Article
Clinical Studies
Schattauer GmbH Stuttgart

Molecular Study of Glanzmann Thrombasthenia in 3 Patients Issued from 2 Different Families

C Vinciguerra
1   The Laboratoire d’Hémobiologie, Institut Pasteur, INSERM U331, Lyon, France
,
M C Trzeciak
1   The Laboratoire d’Hémobiologie, Institut Pasteur, INSERM U331, Lyon, France
,
N Philippe
2   The Hôpital Debrousse, Lyon, France
,
D Frappaz
3   The Hôpital Nord, Saint Etienne, France
,
J Reynaud
3   The Hôpital Nord, Saint Etienne, France
,
M Dechavanne
1   The Laboratoire d’Hémobiologie, Institut Pasteur, INSERM U331, Lyon, France
,
C Negrier
1   The Laboratoire d’Hémobiologie, Institut Pasteur, INSERM U331, Lyon, France
› Author Affiliations
Further Information

Publication History

Received 17 May 1994

Accepted after resubmission 20 April 1995

Publication Date:
09 July 2018 (online)

Summary

In an effort to further understand Glanzmann thrombasthenia (GT) 3 patients from 2 different families were studied. After biochemical and immunological analysis these patients were classified as type I. We observed in the first family a new restriction site for Stu I in exon II of the glycoprotein (GP) Ilia gene caused by a homozygous nonsense mutation: 62 Arg to stop codon. The parents were heterozygotes for this mutation. We found in the second family a previously described nonsense mutation: 584 Arg to stop codon in exon 17 of the GPIIb gene. The father and his two affected sons were heterozygous for this genetic defect. This mutation 62 Arg to stop codon is a new description of a genetic defect associated with GT. Furthermore, the discovery of the same mutation in 3 affected families from different ethnic groups raises the possibility of either a hot spot mutation in the CG dinucleotide region of GPIIb gene, or an ancient mutant allele present in diffuse populations at a relatively high frequency

 
  • References

  • 1 Nurden AT, Caen JP. An abnormal platelet glycoprotein pattern in three cases of Glanzmann’s thrombasthenia. Br J Haematol 1974; 28: 253-260
  • 2 Hynes RO. Integrins: a family of cell surface receptors. Cell 1987; 48: 549-554
  • 3 D’Souza SE, Ginsberg MH, Burke TA, Lam SC T, Plow EF. Localization of an Arg-Gly-Asp recognition site within an integrin adhesion receptor. Science 1988; 242: 91-93
  • 4 Lam SC T, Plow EF, Smith MA, Andrieux A, Ryckwaert JJ, Marguerie G, Ginsberg MH. Evidence that arginyl-glycyl-aspartate peptides and fibrinogen γ-chain peptides share a common binding site on platelets. J Biol Chem 1987; 262: 947-950
  • 5 Bray PF, Rosa JP, Johnston GI, Shiu DT, Cook RG, Lau C, Kan YW, McEver RP, Shuman MA. Platelet glycoprotein lib, chromosomal localization and tissue expression. J Clin Invest 1987; 80: 1812-1817
  • 6 Cong NVan, Uzan G, Gross MS, Jegou-Foubert C, Frachet P, Boucheix C, Marguerie G, Frezal J. Assignment of human platelet GP2B (GPIIb) gene to chromosome 17, region q21.1-q21.3. Hum Genet 1988; 80: 389-392
  • 7 Rosa JP, Bray PF, Gayet O, Johnston GI, Cook RG, Jackson KW, Shuman MA, McEver RP. Cloning of glycoprotein Ilia cDNA from human erythro- leukemia cells and localization of the gene to chromosome 17. Blood 1988; 72: 593-600
  • 8 Heidenreich R, Eisman R, Surrey S, Delgrosso K, Bennet JS, Schwartz E, Poncz M. Organization of the gene for platelet glycoprotein lib. Biochemistry 1990; 29: 1232-1244
  • 9 Lanza F, Kieffer N, Phillips DR, Fitzgerald A. Characterization of the human platelet glycoprotein Ilia gene. J Biol Chem 1990; 265: 18098-18103
  • 10 Zimrin AB, Gidwitz S, Lord S, Schwartz E, Bennet JS, White GC, Poncz M. The genomic organization of platelet glycoprotein Ilia. J Biol Chem 1990; 265: 8590-8595
  • 11 Bray PF, Rosa JP, Lingappa VR, Kan YW, McEver RP, Shuman MA. Biogenesis of the platelet receptor lor fibrinogen: evidence lor separate precursors for glycoproteins IIb and IIIa. Proc Natl Acad Sci USA 1986; 83: 1480-1484
  • 12 Duperray A, Troesch A, Berthier R, Chagnon E, Frachet P, Uzan G, Marguerie G. Biosynthesis and assembly of platelet GPIIb-IIIa in human megakaryocytes: evidence that assembly between Pro-GPIIb and GPU la is a prerequisite for expression of the complex on the cell surface. Blood 1989; 74: 1603-1611
  • 13 O’Toole TP, Loftus JC, Plow EF, Glass AA, Harper JR, Ginsberg MH. Efficient surface expression of platelet GPIIb-IIIa requires both subunits. Blood 1989; 74: 14-18
  • 14 Caen JP. Glanzmann’s thrombasthenia. Clin Haematol 1972; 1: 383-392
  • 15 George JN, Nurden AT, Phillips DR. Molecular defects in interactions of platelets with the vessel wall. N Engl J Med 1984; 311: 1084-1095
  • 16 George JN, Caen JP, Nurden AT. Glanzmann’s thrombasthenia: the spectrum of clinical disease. Blood 1990; 75: 1383-1395
  • 17 Southern E. Detection of specific sequences among DNA fragments. J Mol Biol 1975; 98: 503-517
  • 18 Gu JM, Xu WF, Wang XD, Wu QY, Chi CW, Ruan CG. Identification of a nonsense mutation at amino acid 584-arginine of platelet glycoprotein IIb in patients with type I Glanzmann thrombasthenia. Br J Haematol 1993; 83: 442-449
  • 19 Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987; 162: 156
  • 20 Lyman S, Aster RH, Visentin GP, Newman PJ. Polymorphism of human platelet membrane glycoprotein lib associated with the BaK(a)/BaK(b) alloantigen system. Blood 1990; 75: 2343-2348
  • 21 Newman PJ, Gorski J, White GC, Gidwitz S, Cretney CJ, Aster RH. Enzymatic amplification of platelet-specific messenger RNA using the polymerase chain reaction. J Clin Invest 1988; 82: 739-743
  • 22 Sanger F, Nicklen S, Coulson A. DNA sequencing with chain-termination inhibitors. Proc Natl Acad Sci USA 1977; 74: 5463-7
  • 23 Russel ME, Seligsohn U, Coder BS, Ginsberg MH, Skoglund P, Quertermous T. Structural integrity of the glycoprotein IIb and IIIa genes in Glanzmann thrombasthenia patients from Israel. Blood 1988; 72: 1833-1836
  • 24 Bray PF, Shuman MA. Identification of an abnormal gene for the GPU la subunit of the platelet fibrinogen receptor resulting in Glanzmann’s thrombasthenia. Blood 1990; 75: 881-888
  • 25 Li L, Bray PF. Homologous recombination among three intragene Alu sequences causes an inversion-deletion resulting in the hereditary bleeding disorder Glanzmann thrombasthenia. Am J Human Genet 1993; 53: 140-149
  • 26 Burk CD, Newman PJ, Lyman S, Gill J, coller BS, Poncz M. A deletion in the gene for glycoprotein lib associated with Glanzmann’s thrombasthenia. J Clin Invest 1991; 87: 270-276
  • 27 Kato A, Yamamoto K, Miyazaki S, Jung S, Moroi M, Aoki N. Molecular basis for Glanzmann’s thrombasthenia (GT) in a compound hetcrozygotc with glycoprotein lib gene: a proposal for the classification of GT based on the biosynthetic pathway of glycoprotein llb-llla. Blood 1992; 79: 3212-3218
  • 28 Newman PJ, Seligsohn U, Lyman S, Coiler BS. The molecular genetic basis of Glanzmann thrombasthenia in the Iraqi-Jewish anil Arab populations in Israel. Proc Natl Acad Sci USA 1991; 88: 3160-3164
  • 29 Jin Y, Dietz HC, Nurden A, Bray PF. Single-strand conformation polymorphism analysis is a rapid and effective method for the identification of mutations and polymorphisms in the gene for glycoprotein Illa. Blood 1993; 82: 2281-2288
  • 30 Dietz HC, Valle D, Francomano CA, Kendzior RJ, Pycritz RE, Cutting GR. The skipping of constitutive exons in vivo induced by nonsense mutations. Science 1993; 259: 680-683
  • 31 Rosa JP, Me Ever RP. Processing and assembly of the integrin, glycoprotein llb-llla in HEL cells. J Biol Chem 1989; 264: 12596-12603
  • 32 Chen YP, Djaflar I, Pidard D, Steiner B, Cieutat AM, Caen JP, Rosa JP. Scr-752 Pro mutation in the cytoplasmic domain of integrin subunit and defective activation of platelet integrin αhbβ3(glycoprotein llb-llla) in a variant of Glanzmann thrombasthenia. Proc Natl Acad Sci USA 1992; 89: 10169-10173
  • 33 Iwamoto S, Nishiumi E, Kajii E, Ikcmoto S. An exon 28 mutation resulting in alternative splicing of the glycoprotein lib transcript and Glanzmann’s thrombasthenia. Blood 1994; 83: 1017-1023
  • 34 Burk C, Ingram C, Weiner M, Rappaport EF, Schwartz E, Poncz M. A Taq I polymorphism for the human platelet glycoprotein IIIa gene (GP3a). Nucleic Acids Res 1988; 16: 7216
  • 35 Ruan C, Gu J, Wang X, Chu X, Pan J. Application of GPIIIa gene Taq I polymorphism to determination of carrier status in Glanzmann’s thrombasthenia families of Chinese origin. Thromb Haemost 1993; 69: 64-69
  • 36 Bray PF, Barsh G, Rosa JP, Luo XY, Magenis E, Shuman MA. Physical linkage of the genes for platelet membrane glycoproteins IIb and Ilia. Proc Natl Acad Sci USA 1988; 85: 8686-8687