Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity

@article{Kokame2002MutationsAC,
  title={Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity},
  author={K. Kokame and M. Matsumoto and K. Soejima and H. Yagi and H. Ishizashi and M. Funato and H. Tamai and M. Konno and K. Kamide and Y. Kawano and T. Miyata and Y. Fujimura},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  year={2002},
  volume={99},
  pages={11902 - 11907}
}
von Willebrand factor (VWF) is synthesized primarily in vascular endothelial cells and secreted into the plasma as unusually large VWF multimers. Normally, these multimers are quickly degraded into smaller forms by a plasma metalloproteinase, VWF-cleaving protease (VWF-CP). Decreases in the activity of this enzyme result in congenital and acquired thrombotic thrombocytopenic purpura (TTP). The human VWF-CP has recently been purified. Cloning of the corresponding cDNA revealed that the 1,427-aa… Expand
Von-Willebrand Factor Cleaving Protease (ADAMTS-13) Activity in Various Thrombotic, Hemolytic and Autoimmune Disorders
TLDR
It is demonstrated, that congenital TTP is caused by mutations in the gene responsible for the production of vWF cleaving protease, and the specificity of ADAMTS-13 deficiency for acute TTP has been challenged by findings of low activity in physiological and pathological conditions other than TTP. Expand
Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13.
TLDR
The VWF-cleaving proteinase activity of the truncated enzyme was comparable to that of the wild-type enzyme but its secretion from transfected COS-7 cells was about 14% of theWild type. Expand
Interplay between ADAMTS13 and von Willebrand factor in inherited and acquired thrombotic microangiopathies.
TLDR
ADAMTS13 helps maintain vascular homeostasis by preventing the excess thrombus formation and is likely that the cysteine-rich/spacer domains are essential for VWF cleavage and are the principal epitopes recognized by autoantibodies in patients with acquired TTP. Expand
ADAMTS13 gene mutation in congenital thrombotic thrombocytopenic purpura with previously reported normal VWF cleaving protease activity.
TLDR
All the cases of hereditary TTP studied by DNA sequence analysis to date appear to be due to mutations within the ADAMTS13 gene. Expand
Dissociation between the level of von Willebrand factor‐cleaving protease activity and disease in a patient with congenital thrombotic thrombocytopenic purpura
TLDR
Observations suggest that there are other factors in conjunction with severe deficiency of VWF protease activity that participate in the platelet‐mediated thrombotic complications and other disease manifestations of congenital TTP, and it is possible that splenectomy could be an effective treatment option for some patients with severe, congenitals TTP. Expand
VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS-13.
TLDR
ADAMTS-13 was recently identified as a new hemostatic factor, von Willebrand factor (VWF)-cleaving protease, and data suggested that a minimal region as a functional substrate consisted of 73 amino acid residues from D1596 to R1668 of VWF, designated VWF73, and that further deletion of the E1660-R1668 region led to the loss of cleavage by ADAMts-13. Expand
Mutation analysis and clinical implications of von Willebrand factor-cleaving protease deficiency.
TLDR
It is confirmed that deficiency of ADAMTS13 is a molecular mechanism responsible for familial TTP and an early diagnosis allows prophylactic treatment with fresh plasma infusions. Expand
Ten candidate ADAMTS13 mutations in six French families with congenital thrombotic thrombocytopenic purpura (Upshaw–Schulman syndrome)
TLDR
It is suggested that several structural domains of this metalloprotease are involved in both its biogenesis and its substrate recognition process. Expand
Expression and characterization of recombinant human ADAMTS-13.
TLDR
Recent advances in cell culture expression and functional characterization of human rADAMTS-13 raise the prospect of developing a recombinant substitution therapy to improve TTP treatment and allowing present diagnostic assays to be simplified. Expand
Mechanisms of the interaction between two ADAMTS13 gene mutations leading to severe deficiency of enzymatic activity
TLDR
The mechanism and mechanistic effects of the mutations were explored by means of differential immunofluorescence, that demonstrated an homogeneous distribution of ADAMTS13WT in the Cis‐Golgi and endoplasmic reticulum (ER) compartments, and a reduction of ADamTS13Val88Met in both compartments. Expand
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TLDR
The 4.6-kilobase pair cDNA sequence for VWFCP has been determined and may have functional significance, producing proteins with distinct abilities to interact with cofactors, connective tissue, platelets, and von Willebrand factor. Expand
Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening systemic illness of abrupt onset and unknown cause. Proteolysis of the blood-clotting protein von Willebrand factor (VWF) observed inExpand
Deficient Activity of von Willebrand Factor–Cleaving Protease in Chronic Relapsing Thrombotic Thrombocytopenic Purpura
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TLDR
Successful purification of vWF-CPase revealed that this enzyme is composed of a single polypeptide with a molecular mass of approximately 190 kd, and its complementary DNA cloning unambiguously indicated that it is uniquely produced in the liver and its gene is located on chromosome 9q34. Expand
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TLDR
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TLDR
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TLDR
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