A Type 2b von Willebrand Disease Mutation (lle546→Val) Associated with an Unusual Phenotype

A B Federici; P M Mannucci; F Stabile; M T Canciani; N Di Rocco; S Miyata; J Ware; Z M Ruggeri

doi:10.1055/s-0038-1657699

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1997; 78(03): 1132-1137
DOI: 10.1055/s-0038-1657699

Rapid Communication

Schattauer GmbH Stuttgart

A Type 2b von Willebrand Disease Mutation (lle⁵⁴⁶→Val) Associated with an Unusual Phenotype

Authors

A B Federici

¹The Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milano, Italy
P M Mannucci

¹The Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milano, Italy
F Stabile

¹The Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milano, Italy
M T Canciani

¹The Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milano, Italy
N Di Rocco

¹The Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milano, Italy
S Miyata

²The Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine and Department of Vascular Biology, The Scripps Research Institute, La Jolla, CA, USA
J Ware

²The Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine and Department of Vascular Biology, The Scripps Research Institute, La Jolla, CA, USA
Z M Ruggeri

²The Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine and Department of Vascular Biology, The Scripps Research Institute, La Jolla, CA, USA

Abstract

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Summary

Type 2B von Willebrand disease (vWD) is typically characterized by enhanced ristocetin-induced platelet aggregation (RIPA) caused by increased von Willebrand factor (vWF) affinity for platelets. Furthermore, absence of larger vWF multimers in plasma is characteristic of the originally described type IIB patients, now considered a subgroup of type 2B. We describe here three affected members of a family presenting with prolonged bleeding time, thrombocytopenia, markedly enhanced RIPA and spontaneous platelet aggregation, but normal plasma vWF antigen and ristocetin cofactor activity. Larger plasma vWF multimers, albeit decreased, were present in relatively greater proportion than in other type IIB patients. Genetic studies performed in two of these patients resulted in the identification of a previously unreported A→G transition at nucleotide 4175 in the sequence of the pre-pro-vWF cDNA, corresponding to the substitution Ile^546→Val in the mature vWF subunit. This mutation appears to be responsible for an unusual type 2B phenotype, with greater enhancement of the vWF platelet interaction than in typical cases but partial preservation of the larger vWF multimers in plasma.

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References

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