Characterisation of Type 2N von Willebrand Disease Using Phenotypic and Molecular Techniques

I M Nesbitt; A C Goodeve; A M Guilliatt; M Makris; F E Preston; I R Peake

doi:10.1055/s-0038-1650401

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1996; 75(06): 959-964
DOI: 10.1055/s-0038-1650401

Original Article

Schattauer GmbH Stuttgart

Characterisation of Type 2N von Willebrand Disease Using Phenotypic and Molecular Techniques

Authors

I M Nesbitt

The Sections of Molecular Genetics and Haematology, Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, UK
A C Goodeve

The Sections of Molecular Genetics and Haematology, Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, UK
A M Guilliatt

The Sections of Molecular Genetics and Haematology, Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, UK
M Makris

The Sections of Molecular Genetics and Haematology, Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, UK
F E Preston

The Sections of Molecular Genetics and Haematology, Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, UK
I R Peake

The Sections of Molecular Genetics and Haematology, Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, UK

Abstract

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Summary

von Willebrand factor (vWF) is a multimeric glycoprotein found in plasma non covalently linked to factor VIII (FVIII). Type 2N von Willebrand disease (vWD) is caused by a mutation in the vWF gene that results in vWF with a normal multimeric pattern, but with reduced binding to FVIII.

We have utilised methods for the phenotypic and genotypic detection of type 2N vWD. The binding of FVIII to vWF in 69 patients, 36 with type 1 vWD, 32 with mild haemophilia A and one possible haemophilia A carrier with low FVIII levels was studied. Of these, six were found to have reduced binding (five type 1 vWD, one possible haemophilia A carrier), DNA was extracted from these patients and exons 18-23 of the vWF gene encoding the FVIII binding region of vWF were analysed. After direct sequencing and chemical cleavage mismatch detection, a Thr28Met mutation was detected in two unrelated individuals, one of whom appears to be a compound heterozygote for the mutation and a null allele. No mutations were found in the region of the vWF gene encoding the FVIII binding region of vWF in the other four patients

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References

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