Gly197Arg mutation in protein C causes recurrent thrombosis in a heterozygous carrier.

ABSTRACT:

Background

Activated protein C (APC) downregulates thrombin generation by inactivating procoagulant cofactors Va and VIIIa by limited proteolysis. We identified two protein C-deficient patients both of whom carry a heterozygous Gly197 to Arg (G197R) mutation in PROC and experience venous thrombosis.

Objective

The objective of this study was to determine the molecular basis of the clotting defect in patients carrying the G197R mutation.

Methods

We expressed protein C-G197R in mammalian cells and characterized its properties in established coagulation and anti-inflammatory assay systems.

Results

The activation of protein C-G197R by thrombin was improved ~10-fold; however, its activation by thrombin was not promoted by thrombomodulin (TM). In a tissue factor-media

SUBMITTER: Lu Y 

PROVIDER: S-EPMC7192786 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature