Identifying potential mutations responsible for cases of pulmonary arterial hypertension

Abstract

Pulmonary Arterial Hypertension (PAH) is a progressive and devastating disease for which there is an escalating body of genetic and related pathophysiological information on disease pathobiology. Nevertheless, the success to date in identifying susceptibility genes, genetic variants and epigenetic processes has been limited due to PAH clinical multi-faceted variations. A number of germline gene candidates have been proposed but demonstrating consistently the association with PAH has been problematic, at least partly due to the reduced penetrance and variable expressivity. Although the data for bone morphogenetic protein receptor type 2 (BMPR2) and related genes remains undoubtedly the most extensive, recent advanced gene sequencing technologies have facilitated the discovery of further gene candidates with mutations among those with and without familial forms of PAH. An in depth understanding of the multitude of biologic variations associated with PAH may provide novel opportunities for therapeutic intervention in the coming years. This knowledge will irrevocably provide the opportunity for improved patient and family counseling as well as improved PAH diagnosis, risk assessment, and personalized treatment.