A new variant of Bernard-Soulier syndrome characterized by dysfunctional glycoprotein (GP) Ib and severely reduced amounts of GPIX and GPV

Patrizia Noris, Eloisa Arbustini, Pierangelo Spedini, Simona Belletti, Carlo Luigi Balduini

Research output: Contribution to journalArticle

Abstract

We describe a new variant of Bernard-Soulier syndrome characterized by almost normal amounts of GPIb and severely reduced GPIX and GPV. Despite surface expression, GPIbα failed to support ristocetin-induced platelet agglutination and to bind two conformation-dependent monoclonal antibodies, suggesting a qualitative defect. Sequence analysis of the gene coding for GPIX revealed a T-to-C substitution at base 1811, leading to a Leu40Pro conversion, whereas no defects were found in the coding region of the GPIbα gene. Allele-specific restriction enzyme analysis showed that the propositus and one of his sisters, both with severe bleeding diathesis, were homozygous for the GPIX mutation; the members of the family with mild bleeding diathesis and/or giant platelets in the peripheral blood were heterozygous, whereas the healthy ones were homozygous for the normal alelle. Infusion of 1-desamino- 8-D-arginine vasopressin normalized bleeding time in the two severely affected patients, although it did not modify ristocetin-induced platelet agglutination or membrane expression of GPIbα, GPIX, GPIIb-IIIa and GMP- 140. Moreover, in one patient, normalization of bleeding time and rise of yon Willebrand factor plasma concentration did not seem to be directly related.

Original languageEnglish
Pages (from-to)1004-1013
Number of pages10
JournalBritish Journal of Haematology
Volume103
Issue number4
DOIs
Publication statusPublished - 1998

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Keywords

  • Bernard-Soulier syndrome
  • DDAVP
  • Platelet glycoproteins

ASJC Scopus subject areas

  • Hematology

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