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

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 oxidored...

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Published in:Journal of hematology and oncology 2015-06, Vol.8 (1), p.73-73, Article 73
Main Authors: Yin, Jie, Ma, Zhenni, Su, Jian, Wang, Jiong-Wei, Zhao, Xiaojuan, Ling, Jing, Bai, Xia, Ouyang, Wanyan, Wang, Zhaoyue, Yu, Ziqiang, Ruan, Changgeng
Format: Article
Language:English
Subjects:
Analysis
Gene mutations
Genetic aspects
HEK293 Cells
Humans
Letter to the Editor
Mutation
Transfection
Von Willebrand factor
von Willebrand Factor - genetics
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Summary: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.
ISSN:1756-8722
1756-8722
DOI:10.1186/s13045-015-0166-9