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Mechanisms of the interaction between twoADAMTS13 gene mutations leading to severe deficiency of enzymatic activity by Flora Peyvandi; Silvia Lavoretano; Roberta Palla; Carla Valsecchi; Giuliana Merati; Raimondo De Cristofaro; Edoardo Rossi; Pier Mannuccio Mannucci is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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## Communicated by Arupa Ganguly The inherited deficiency of the von Willebrand factor-cleaving protease ADAMTS13 is associated with rare forms of thrombotic thrombocytopenic purpura (TTP). We investigated a woman with a family history of chronic recurrent TTP and undetectable plasma levels of ADAMTS13 activity. Genetic analysis revealed two missense mutations in the heterozygous state: p.Val88Met substitution in the metalloprotease domain and p.Gly1239Val substitution in the first CUB domain of ADAMTS13. To explore the mechanism of ADAMTS13 deficiency in this patient, the wild type (WT; ADAMT13 WT ) and each mutant construct (ADAMTS13 Val88Met , ADAMTS13 Gly1239Val ) were transiently expressed in HEK 293 and COS-7 cells. To recapitulate the compound heterozygous state of the patient, both mutant ADAMTS13 proteins were also expressed together. The p.Val88Met mutation led to a defect of secretion of the protease associated with a reduction of enzymatic activity, the p.Gly1239Val mutation led to a secretion defect causing intracellular accumulation of the protease. The mechanistic effects of the mutations were further explored by means of differential immunofluorescence, that demonst

Who reads Mechanisms of the interaction between twoADAMTS13 gene mutations leading to severe deficiency of enzymatic activity?

Author

Flora Peyvandi; Silvia Lavoretano; Roberta Palla; Carla Valsecchi; Giuliana Merati; Raimondo De Cristofaro; Edoardo Rossi; Pier Mannuccio Mannucci

Publisher

Hindawi Limited

Published

2006

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)