Type 2N von Willebrand Disease: Rapid Genetic Diagnosis of G2811A (R854Q), C2696T (R816W), T2701A (H817Q) and G2823T (C858F) – Detection of a Novel Candidate Type 2N Mutation: C2810T (R854W)

D. J. Bowen; G. R. Standen; C. Mazurier; C. Gaucher; A. Cumming; S. Keeney; J. Bidwell

doi:10.1055/s-0037-1615134

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1998; 80(01): 32-36
DOI: 10.1055/s-0037-1615134

Rapid Communication

Schattauer GmbH

Type 2N von Willebrand Disease: Rapid Genetic Diagnosis of G2811A (R854Q), C2696T (R816W), T2701A (H817Q) and G2823T (C858F) – Detection of a Novel Candidate Type 2N Mutation: C2810T (R854W)

D. J. Bowen

¹Arthur Bloom Center, Dept of Haematology, University of Wales College of Medicine, Heath Park, Cardiff, S Wales, UK

,

G. R. Standen

²Molecular Haematology Unit, Dept of Haematology, Bristol Royal Infirmary, Bristol, UK

,

C. Mazurier

³Laboratoire de Recherche sur l’Hémostase, LFB, Lille, France

,

C. Gaucher

³Laboratoire de Recherche sur l’Hémostase, LFB, Lille, France

,

A. Cumming

⁴Dept of Clinical Haematology, The Royal Infirmary, Manchester, UK

,

S. Keeney

⁴Dept of Clinical Haematology, The Royal Infirmary, Manchester, UK

,

J. Bidwell

⁵Dept of Pathology and Microbiology, University of Bristol, Bristol, UK

› Institutsangaben

Abstract

Summary

The majority of patients with type 2N von Willebrand disease (VWD type 2N) have mutations in the region of the von Willebrand factor (VWF) gene encoding the factor VIII binding domain of VWF. Two mutations predominate among VWD type 2N patients: G2811A and C2696T, which respectively bring about the amino acid substitutions R854Q and R816W in VWF. Several other mutations have been found in VWD type 2N, including T2701A (H817Q) and G2823T (C858F). We have developed a genetic test which permits rapid screening for these four mutations in a single polymerase chain reaction (PCR). The test employs induced heteroduplex formation using two universal heteroduplex generators, one of which detects G2811A (R854Q) and G2823T (C858F), the other detects C2696T (R816W) and T2701A (H817Q). The allele frequency of the common G2811A (R854Q) mutation was investigated in the local (S. Wales) population by examination of 216 VWF genes (108 individuals) and was found to be 0.01. The heteroduplex-based test additionally detected a novel candidate type 2N mutation, C2810T (R854W) and a previously described polymorphism, G2805A (R852Q). The polymorphism showed allele frequencies of 0.92 (G nucleotide) and 0.08 (A nucleotide) in the population study.

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