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DOI: 10.1055/s-0037-1614030
A New Candidate Missense Mutation (Leu 1657 Ile) in an Apparently Asymptomatic Type 2A (Phenotype IIA) von Willebrand Disease Family
Publikationsverlauf
Received
14. Dezember 1999
Accepted after revision
10. April 2000
Publikationsdatum:
14. Dezember 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200003/lookinside/thumbnails/10-1055s-0037-1614030-1.jpg)
Summary
Type 2A von Willebrand disease (VWD) is mostly an autosomal dominantly inherited bleeding disorder characterised by a qualitative defect of von Willebrand factor (VWF). Mutation screening was used to screen the whole of VWF gene followed by direct sequencing to detect the mutation in a father and son diagnosed with type 2A (phenotype IIA) von Willebrand disease. A C5219 to A transversion was detected predicting Leucine to Isoleucine substitution in codon 1657. This novel missense mutation which was also identified by MboI restriction enzyme analysis, was found in both patient and his father but not in any other unaffected family member or 50 unrelated normal individuals. This substitution was reproduced by in vitro site directed mutagenesis of full-length VWF cDNA and transiently expressed in COS-7 cells. The corresponding recombinant VWF protein exhibited the full spectrum of VWF multimers, suggesting that the abnormal multimer seen in the patient results from increased proteolysis.
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