Mutations in the D1 domain of von Willebrand factor impair their propeptide-dependent multimerization, intracellular trafficking and secretion

作者：Jie Yin, Zhenni Ma, Jian Su, Jiong‐Wei Wang, Xiaojuan Zhao, Jing Ling, Xia Bai, Wanyan Ouyang, Zhaoyue Wang, Ziqiang Yu, Changgeng Ruan · 发表于：Journal of Hematology & Oncology · 年份：2015 · DOI：10.1186/s13045-015-0166-9 · 被引用次数：14 · 研究领域：Platelet Disorders and Treatments、Blood groups and transfusion、Blood disorders and treatments

We identified three novel mutations (p.Gly39Arg, p.Lys157Glu, p.Cys379Gly) and one previously known mutation (p.Asp141Asn) in the von Willebrand factor propeptide from three von Willebrand disease patients. All four mutations impaired multimerization of von Willebrand factor, due to reduced oxidoreductase activity of isomeric propeptide. These mutations resulted in the endothelial reticulum retention and impaired basal and stimulated secretions of von Willebrand factor. Our results support that the mutations in the D1 domain lead to defective multimerization, intracellular trafficking, and secretion of von Willebrand factor and result in bleeding of patients.