The molecular genetics of familial venous thrombosis

Abstract

This study of naturally occurring mutations predisposing to venous thrombosis has led to a number of important advances in our understanding of protein structure and function relationships and the molecular basis of gene mutation. It has also potentiated the accurate and reliable presymptomatic and antenatal detection of predisposing gene lesions. Perhaps the major challenge facing us is the probabilistic nature of thromboembolism; only a certain proportion of patients with recognized gene defects predisposing to thrombosis will actually suffer from thrombotic episodes. Environmental insults of various kinds, and perhaps epistatic effects resulting from the influence of other loci, are likely to be contributory factors and will help to determine whether a thrombotic event occurs in individuals already compromised by a defect in a gene whose malfunction is known to predispose to thrombosis. Since molecular genetic techniques allow us to dissect the allelioheterogeneity of the different deficiency states by characterizing the wide spectrum of gene mutations giving rise to thrombosis, it may eventually prove possible to relate specific gene lesions to the probability of thromboembolism as well as to the severity and frequency of thrombotic episodes. The multifactorial nature of thrombosis demands a multidisciplinary approach to the analysis of its causation, early detection, treatment and prevention. The application of the new and powerful techniques of molecular genetics promises to make a substantial contribution to all aspects of thrombosis research.