Molecular genetics of familial venous thrombosis

Mutations in a variety of human genes are now known to predispose to venous thrombosis. Study of these mutations has led to important advances in our understanding of the structure and function of haemostatic regulatory proteins and has facilitated accurate presymptomatic and antenatal diagnosis. However, owing to the probabilistic nature of thromboembolism, only a certain proportion of patients with a recognized gene defect in the heterozygous state will actually suffer from thrombotic episodes. Allelic heterogeneity, epistatic effects resulting from the influence of other loci and environmental insults of various kinds all play a role in determining whether a thrombotic event occurs in individuals already compromised by a gene defect. Nevertheless, characterization of the wide spectrum of gene mutations giving rise to thrombosis may allow us to relate specific gene lesions to the probability of thromboembolism as well as to the severity and frequency of thrombotic episodes.