Characterization of immune cells and perforin mutations in familiar venous thromboembolism.

This study was to carry out exome sequencing in a Han Chinese family with venous thromboembolism.Three venous thromboembolism (VTE) patients and five members from a Han Chinese family were evaluated by exome sequencing.Among the 3 VTE patients, mutations of 2 genes including PRF1 and HTR2A were identified and predicted to be functionally damaged to their encoded proteins. In addition, the PRF1 mutation and the HTR2A mutation identified in our study were absent in 100 non-related controls, indicating that venous thromboembolism has a genetic component. The R357W mutation is located in the membrane attack complex/perforin domain of PRF1 protein, which exists in both the perforin. The steps of killing foreign or pathological antigen cells by NK cells, CD8 (+)T cells and the membrane attack complex include membrane perforation and release of the granzyme, either of which is abnormal can lead to immune dysfunction.The mutations of immune related genes in familial VTE might provide new understanding of the pathogenesis of familial venous thromboembolism.