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Variant Bernard-Soulier syndrome type bolzano. A congenital bleeding disorder due to a structural and functional abnormality of the platelet glycoprotein Ib-IX complex

Academic Article
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Overview

authors

  • Demarco, L.
  • Mazzucato, M.
  • Fabris, F.
  • Deroia, D.
  • Coser, P.
  • Girolami, A.
  • Vicente, V.
  • Ruggeri, Zaverio

publication date

  • July 1990

journal

  • Journal of Clinical Investigation  Journal

abstract

  • We have studied a patient with a congenital bleeding disorder and phenotypic manifestations typical of Bernard-Soulier syndrome, including giant platelets with absent ristocetin-induced von Willebrand factor binding. Two monoclonal antibodies reacting with distinct epitopes in the amino-terminal domain of the alpha-chain of glycoprotein (GP) Ib were used to estimate the number of GP Ib molecules on the platelet membrane. In the patient, binding of one antibody (LJ-Ib10) was approximately 50% of normal, while binding of the other (LJ-Ib1) was absent. Binding of both antibodies was reduced to approximately 50% of normal in the mother and one sister of the propositus, and their platelets exhibited approximately 70% of normal von Willebrand factor binding. Immunoblotting studies confirmed the presence of GP Ib alpha, as well as GP IX, in patient platelets. Antibody LJ-Ib10, but not LJ-Ib1, could immunoprecipitate the patient's GP Ib alpha from surface-labeled proteins. Thus, platelets from the propositus contained a structurally and functionally altered GP Ib-IX complex lacking a specific antibody epitope and the ability to bind von Willebrand factor. In contrast, the binding of human alpha-thrombin to the patient's platelets was normal, and three classes of binding sites with high, intermediate, and low affinity could be detected. These studies define a distinct variant form of Bernard-Soulier syndrome and provide evidence, based on a naturally occurring mutant molecule, that the amino-terminal region of GP Ib alpha contains a von Willebrand factor-binding domain distinct from the high affinity thrombin-binding site. Use of different monoclonal antibodies with distinct epitope specificities appears to be essential for a correct identification of variant Bernard-Soulier syndrome.

subject areas

  • Antibodies, Monoclonal
  • Bernard-Soulier Syndrome
  • Blood Platelet Disorders
  • Blotting, Western
  • Epitopes
  • Humans
  • Molecular Weight
  • Platelet Membrane Glycoproteins
  • Precipitin Tests
  • Protein Conformation
  • Thrombin
  • von Willebrand Factor
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Identity

PubMed Central ID

  • PMC296685

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci114692

PubMed ID

  • 1694864
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Additional Document Info

start page

  • 25

end page

  • 31

volume

  • 86

issue

  • 1

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