Disease: Von-willebrand Disease (Vicenza)
Model organism: Mice
Variant: VWF NM_000552.5 c:3614G>A p.(R1205H), E3 module of D3 domain
Patient Phenotypes: enhanced VWF clearance, reduced plasma VWF:Ag ratio (Reduced half-life).
Other substitutions at the R1205 position results in similar enhanced VWF clearance. (Cysteine and Serine) Ref DOIs: (10.1111/jth.12875) (10.1160/TH07-09-0565)
Suggests VWF-R1205 plays a specific roles in regulating VWF clearance in vivo. They authors finding demonstrage significant conformational changes to WVF-D'D3 region. Conformational changes trigger an enhanced macrophage-mediated clearance which is most likely modulated through SR-AI and LRP1 VWF clearance receptors.
