Clinical and genetic features of protein C deficiency in 23 unrelated Chinese patients

Abstract

In this study, we investigated the clinical and genetic features of protein C deficiency in the Chinese population. A total of 23 symptomatic patients with protein C deficiency were identified by thrombophilic assays. Detailed clinical data about the patients with respect to their personal and family history of venous thromboembolism (VTE) were collected. Mutational analysis was then performed by direct sequencing of the protein C gene (PROC) in the patients and their family members. Of the 23 patients, 30.4% (7/23) had additional risk factors, 51.2% (12/23) suffered from recurrent thrombotic episodes, and 50.0% (6/12) of the patients with recurrent thrombosis had more than one heterozygous mutation in PROC itself or combined with protein S gene (PROS). The sex distribution of male:female was 19:4 in the 23 symptomatic patients and 10:2 in the 12 recurrent patients. Almost all patients (22/23) had lower extremity deep vein thrombosis (DVT) and one had pulmonary embolism (PE) only. A total of 15 different causative mutations were identified from the 23 subjects with 6 (40.0%) of the mutations being novel. Among the mutations identified, the Arg147Trp substitution was hotspot mutation in the Chinese population with a high frequency of 43.5%. Our finding suggests that complex genotypes of PROC or combined with protein S deficiency are primarily responsible for an increased risk of recurrent VTE. Our data further provides a framework for correlating the clinical pathogenesis of protein C deficiency to ethnic backgrounds in the Chinese population.