ArticleBlood2010
The mutation N528S in the von Willebrand factor (VWF) propeptide causes defective multimerization and storage of VWF.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 39 citations in OpenAlex.
- Novel cysteine substitution p.(Cys1084Tyr) causes variable expressivity of qualitative and quantitative VWF defects.Blood advances · 2022Article
- Review
- Angiodysplasia in von Willebrand Disease: Understanding the Clinical and Basic Science.Seminars in thrombosis and hemostasis · 2017Review
- An Insight into Glyco-Microheterogeneity of Plasma von Willebrand Factor by Mass Spectrometry.Journal of proteome research · 2017Article
- Identification and characterization of the elusive mutation causing the historical von Willebrand Disease type IIC Miami.Journal of thrombosis and haemostasis : JTH · 2016Article
- Mutations in the D'D3 region of VWF traditionally associated with type 1 VWD lead to quantitative and qualitative deficiencies of VWF.Thrombosis research · 2016Article
- Interpreting functional effects of coding variants: challenges in proteome-scale prediction, annotation and assessment.Briefings in bioinformatics · 2016Review
- Article
- [The function and clinical value of Von Willebrand factor propeptide].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2015Article
- Update on von Willebrand factor multimers: focus on high-molecular-weight multimers and their role in hemostasis.Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis · 2014Review
- Identification and characterisation of mutations associated with von Willebrand disease in a Turkish patient cohort.Thrombosis and haemostasis · 2013Article
- Insights into pathological mechanisms of missense mutations in C-terminal domains of von Willebrand factor causing qualitative or quantitative von Willebrand disease.Haematologica · 2013Article
- The molecular genetics of von Willebrand disease.Turkish journal of haematology : official journal of Turkish Society of Haematology · 2012Review
- Article
- Functional architecture of Weibel-Palade bodies.Blood · 2011Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
We characterized a consanguineous Turkish family suffering from von Willebrand disease (VWD) with significant mucocutaneous and joint bleeding. The relative reduction of large plasma von Willebrand factor (VWF) multimers and the absent VWF triplet structure was consistent with type 2A (phenotype IIC) VWD. Surprisingly, platelet VWF was completely deficient of multimers beyond the VWF protomer, suggesting defective alpha-granular storage of larger multimers. Patients were nearly unresponsive to desmopressin acetate, consistent with a lack of regulated VWF release from endothelial cell Weibel-Palade bodies, suggesting defective storage also in endothelial cells. We identified an N528S homozygous mutation in the VWF propeptide D2 domain, predicting the introduction of an additional N-glycosylation site at amino acid 526 in close vicinity to a "CGLC" disulphide isomerase consensus sequence. Expression studies in mammalian cells demonstrated that N528S-VWF was neither normally multimerized nor trafficked to storage granules. However, propeptide containing the N528S mutation trafficked normally to storage granules. Our data indicate that the patients' phenotype is the result of defective multimerization, storage, and secretion. In addition, we have identified a potentially novel pathogenic mechanism of VWD, namely a transportation and storage defect of mature VWF due to defective interaction with its transporter, the mutant propeptide.
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