The molecular biology of von Willebrand disease

Keeney, S.; Cumming, A. M.

doi:10.1046/j.1365-2257.2001.00400.x

Cited by 50 publications

(38 citation statements)

References 231 publications

(301 reference statements)

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“…Type 1 and type 3 are quantitative defects, with type 1 displaying a reduction and type 3 a total absence of the VWF protein. In contrast, the four type 2 variants are all qualitative VWF defects (Keeney & Cumming, 2001).…”

Section: Introductionmentioning

confidence: 99%

Variation in the VWF Gene in Swedish Patients with Type 1 von Willebrand Disease

Johansson

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et al. 2011

Annals of Human Genetics

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SummaryThe spectrum of mutations in the von Willebrand factor (VWF) gene in a Swedish type 1 von Willebrand disease (VWD) population was investigated. To gain more knowledge about the dynamics of VWD mutations, the data were analyzed from a population genetics perspective. The VWF gene was resequenced in 54 Swedish patients diagnosed with type 1 VWD. Fifty-five variable sites were located in exons, 10 in the promoter and 38 in introns. The spectrum of mutations was similar to a European study, but included 10 new candidate mutations. The synonymous sites were evenly distributed along the coding sequence, whereas nonsynonymous sites were located into three clusters. Overall, 44% of patients had no mutations or candidate mutations and no promoter haplotype was significantly associated with disease. In 11 patients (20%), more than one mutation or candidate mutation was detected. The allelic identity for the putative disease-causing mutations was approximately 0.1, compatible with an overall disease frequency of 1%. VWF sequences for exon 28 from eight monkey species were compared with the variable positions found in our patients. Positions classified as mutations were overrepresented among sites that were fixed in all eight monkey species. No general increase of the mutation rate was found for the pseudogene region.

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Section: Introductionmentioning

confidence: 99%

Variation in the VWF Gene in Swedish Patients with Type 1 von Willebrand Disease

Johansson

Halldén

Säll

et al. 2011

Annals of Human Genetics

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“…At the moment, there is no genotypic classification of vWD available. More than 250 mutations of all vWD types have been identified (Keeney and Cumming 2001). The analysis of vWF multimers by electrophoretic separation and subsequent visualization is an important laboratory tool for distinguishing the subtypes of vWD.…”

Section: Introductionmentioning

confidence: 99%

Native multimer analysis of plasma and platelet von Willebrand factor compared to denaturing separation: Implication for the interpretation of satellite bands

et al. 2011

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Blue native electrophoresis (BNE) was applied to analyze the von Willebrand factor (vWF) multimers in their native state and to present a methodology to perform blue native electrophoresis on human plasma proteins, which has not been done before. The major difference between this method and the commonly used SDS‐agarose gel electrophoresis is the lack of satellite bands in the high‐resolution native gel. To further analyze this phenomenon, a second dimension was performed under denaturing conditions. Thereby, we obtained a pattern in which each protein sub‐unit from the first dimension dissociates into three distinct sub‐bands. These bands confirm the triplet structure, which consists of an intermediate band and two satellite bands. By introducing the second dimension, our novel method separates the triplet structure into a higher resolution than the commonly used SDS‐agarose gel electrophoresis does. This helps considerably in the classification of ambiguous von Willebrand's disease subtypes. In addition, our method has the additional advantage of being able to resolve the triplet structure of platelet vWF multimers, which has not been identified previously through conventional SDS‐agarose electrophoresis multimer analysis. This potential enables us to compare the triplet structure from platelet and plasmatic vWF, and may help to find out whether structural abnormalities concern the vWF molecule in the platelet itself, or whether they are due to the physiological processing of vWF shed into circulation. Owing to its resolution and sensitivity, this native separation technique offers a promising tool for the analysis and detection of von Willebrand disorder, and for the classification of von Willebrand's disease subtypes.

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“…[1][2][3] VWF has essential roles in primary hemostasis where it functions in an adhesive matrix between platelets and subendothelial components at sites of vascular injury in vessels subject to high shear stress. 4,5 VWF also acts as a carrier for procoagulant factor VIII (FVIII) in the circulation.…”

Section: Introductionmentioning

confidence: 99%