The mutation N528S in the von Willebrand factor (VWF) propeptide causes defective multimerization and storage of VWF.

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-glycosyl

SUBMITTER: Haberichter SL 

PROVIDER: S-EPMC2881501 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature