ArticleBlood2015
Variable content of von Willebrand factor mutant monomer drives the phenotypic variability in a family with von Willebrand disease.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Functional Characterization of the VWF p.Cys2163Tyr Variant Reveals Impaired Secretion and Intracellular Processing.Biomolecules · 2026Article
- Targeting vascular inflammation and endothelial dysfunction with nanobodies: emerging therapeutic strategies for cardiovascular disease.Frontiers in immunology · 2026Review
- Comparison of genotypes and phenotypes for von Willebrand factor gene variants using Japanese genome database.Blood vessels, thrombosis & hemostasis · 2025Article
- Article
- Conformation-specific RNA aptamers for phenotypic distinction between normal von Willebrand factor and type 2B von Willebrand disease.NAR molecular medicine · 2024Article
- Nanobodies as Diagnostic and Therapeutic Tools for Cardiovascular Diseases (CVDs).Pharmaceuticals (Basel, Switzerland) · 2023Review
- Novel cysteine substitution p.(Cys1084Tyr) causes variable expressivity of qualitative and quantitative VWF defects.Blood advances · 2022Article
- The disulfide bond Cys2724-Cys2774 in the C-terminal cystine knot domain of von Willebrand factor is critical for its dimerization and secretion.Thrombosis journal · 2021Article
- Von Willebrand disease combined with coagulation defects in Iran.Blood transfusion = Trasfusione del sangue · 2021Article
- Laboratory variability in the diagnosis of type 2 VWD variants.Journal of thrombosis and haemostasis : JTH · 2021Article
- Clinical and laboratory phenotype variability in type 2M von Willebrand disease.Journal of thrombosis and haemostasis : JTH · 2017Article
- Enhanced Local Disorder in a Clinically Elusive von Willebrand Factor Provokes High-Affinity Platelet Clumping.Journal of molecular biology · 2017Article
- Variable bleeding phenotype in an Amish pedigree with von Willebrand disease.American journal of hematology · 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
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Von Willebrand disease (VWD) is an inherited bleeding disorder characterized by incomplete penetrance and variable expressivity. We evaluated a 24-member pedigree with VWD type 2 caused by a T>G mutation at position 3911 that predicts a methionine to arginine (M1304R) change in the platelet-binding A1 domain of von Willebrand factor (VWF). This mutation manifests as an autosomal-dominant trait, with clinical and biochemical phenotypic variability among affected individuals, including differences in bleeding tendency and VWF quantity, activity, and multimer pattern. Sequencing of all VWF coding regions in 3 affected individuals did not identify additional mutations. When expressed in heterologous cells, M1304R was secreted in lower quantities, failed to drive formation of storage granules, and was defective in multimerization and platelet binding. When cotransfected in equal quantities with the wild-type complementary DNA, the mutant complementary DNA depressed VWF secretion, although multimerization was only mildly affected. A llama nanobody (AU/VWFa-11) that detects the mutant A1 domain demonstrated highly variable binding to VWF from different affected members, indicating that the VWF contained different percentages of mutant monomers in different individuals. Thus, the observed variability in VWD phenotypes could in part be determined by the extent of mutant monomer incorporation in the final multimer structure of plasma VWF.
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