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A MUTATION IN EXON 27 OF THE VWF GENE CAUSING TYPE 2M AND TYPE 3 VON WILLEBRAND DISEASE IN THREE PATIENTS IN A FAMILY FROM THE WEST OF SCOTLAND
Abstract number: P-T-183
Enayat1 M.S., Guilliatt1 A.M., Alvi2 A., Tait2 C.R., Hill1 F.G.H.
11Haematology, The Birmingham Children Hospital, Birmingham 22Haemophilia and Thrombosis Centre, Royal Infirmary, Glasgow, United Kingdom
How-to-cite Enayat MS, Guilliatt AM, Alvi A, Tait CR, Hill FGH. A MUTATION IN EXON 27 OF THE VWF GENE CAUSING TYPE 2M AND TYPE 3 VON WILLEBRAND DISEASE IN THREE PATIENTS IN A FAMILY FROM THE WEST OF SCOTLAND. J Thromb Haemost 2007; 5 Supplement 2: P-T-183
Abstract
Introduction: von Willebrand Disease (VWD) is characterized by quantitative (type 1 & 3) and qualitative (type 2) deficiencies of von Willebrand Factor (VWF). Reported mutations for type 3 VWD have been scattered throughout the gene but for type 2M VWD have been so far reported in exons 27 and 28 of the VWF gene. We investigated three patients, a mother and one of her daughters with mild and the other daughter with severe bleeding, in a consanguinous family from the West of Scotland.
Methods: Phenotype and multimer analysis were performed using standard methods. Direct DNA sequencing was used to investigate exon 27 and 28 of the VWF gene.
Results: The mother and sister of the proband with discrepant VWF:Ag and VWF:Co and normal multimer were diagnosed with type 2M, while the proband with 0.01 U/ml VWF:Ag was diagnosed type 3 VWD. DNA sequencing revealed a homozygous 3586T>C transition leading to C1196R substitution in exon 27 in the proband, and in heterozygous form in the other 2 affected family members. This mutation has been previously reported once in abstract form (Ref.1), but it is noteworthy that this mutation in homozygous form in our proband has resulted in type 3 VWD.
Conclusions: Although in the C1196R mutation a Cysteine has been replaced by Arginine, it seems in these patients the replacement of Cysteine does not cause abnormal multimer formation and an unstable VWF molecule as seen with other mutations involving this amino acid in the VWF gene. Genetic information from this family demonstrates that a type 2 M VWD mutation in homozygous form can lead to a type 3 VWD phenotype.
References: 1. J.-M. Lavergne, E. Fressinaud, J. Goudemand, M.-M. Horellou, A.-S. Ribba, L. Hilbert, C. Mazurier, D. Mayer. Identification of 5 new Cysteine mutations in the D3 domain of von Willebrand Factor including type 2M von Willebrand disease. Supplement to the journal Thrombosis and Haemostasis, July 2001 (ISSN 0340-6245).
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
Session Details
| Date: |
01/08/2007
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| Time: |
00:00-00:00
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| Session name: |
XXIst ISTH Congress |
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| Location: |
Oxford, UK |
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