Compound Heterozygosity (554-589 del, C515-T Transition) in the Platelet Glycoprotein Ibα Gene in a Patient with a Severe Bleeding Tendency

Maurizio Margaglione; Giovanna D’Andrea; Elvira Grandone; Vincenzo Brancaccio; Aldo Amoriello; Giovanni Di Minno

doi:10.1055/s-0037-1614510

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 81(04): 486-492
DOI: 10.1055/s-0037-1614510

Rapid Communication

Schattauer GmbH

Compound Heterozygosity (554-589 del, C⁵¹⁵-T Transition) in the Platelet Glycoprotein Ibα Gene in a Patient with a Severe Bleeding Tendency

Maurizio Margaglione

¹From the Unit of “Atherosclerosis and Thrombosis”, I.R.C.C.S. “Casa Sollievo della Sofferenza”, S. Giovanni Rotondo, Divisione di Ematologia, Unità di Coagulazione, Università di Palermo, Italy

,

Giovanna D’Andrea

¹From the Unit of “Atherosclerosis and Thrombosis”, I.R.C.C.S. “Casa Sollievo della Sofferenza”, S. Giovanni Rotondo, Divisione di Ematologia, Unità di Coagulazione, Università di Palermo, Italy

,

Elvira Grandone

¹From the Unit of “Atherosclerosis and Thrombosis”, I.R.C.C.S. “Casa Sollievo della Sofferenza”, S. Giovanni Rotondo, Divisione di Ematologia, Unità di Coagulazione, Università di Palermo, Italy

,

Vincenzo Brancaccio

²Centro Trasfusionale, Ospedale “A. Cardarelli”, Napoli, Università di Palermo, Italy

,

Aldo Amoriello

²Centro Trasfusionale, Ospedale “A. Cardarelli”, Napoli, Università di Palermo, Italy

,

Giovanni Di Minno

³Istituto di Medicina Interna e Geriatria, Università di Palermo, Italy

› Author Affiliations

Abstract

Summary

Giant platelets in the blood smear, absent in vitro platelet agglutination in response to ristocetin, and normal aggregation, ATP secretion and thromboxane B₂ formation were found in a young patient with a life-long bleeding tendency. Ristocetin-induced von Willebrand factor binding to her platelets was less than 10% of normal. Flow cytometric analysis with monoclonal antibodies LJ-Ib-1, LJ-Ib-10, and LJ-P3 was consistent with the latter finding. SDS-PAGE analysis of solubilized platelets showed a marked reduction of the platelet glycoprotein (GP) Ibα. Genetic characterisation demonstrated that the patient and her father were heterozygous for a deletion of 36 nucleotides (positions 554-589) leading to a mutant GPIbμ (deletion of aminoacids from residue 169 to 180 and a Glu → Lys substitution at residue 181). In addition, a C → T transition at nucleotide 515 in the other allele of the GPIbα gene was found in the patient and in her mother that results in the substitution of alanine for valine in codon 156 (Bernard-Soulier type Bolzano). These variations occurred within the VI and VII leucine-rich repeats. The novel variant of Bernard-Soulier syndrome identified further suggests that the integrity of leucine-rich repeats is important for normal function of the GP Ib-IX-V receptor complex.

Full Text

References

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