Pre-implantation genetic testing for hereditary pulmonary arterial hypertension: promise and caution

Abstract

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease and most PAH patients have a poor prognosis despite standard-of-care therapies. Heritable PAH (HPAH) is usually (>80%) due to germline mutations in the bone morphogenetic protein receptor 2 ( BMPR2 ) gene [1–4]. Thus, BMPR2 mutations constitute the largest known risk for developing PAH. One of the most perplexing features of HPAH is its reduced penetrance, which confounds genetic counselling. Nearly 80% of mutation carriers have no clinical symptoms, but they can produce offspring that are affected by HPAH [5]. Thus, disease development cannot be predicted in a mutation carrier and this deficiency in our knowledge about disease penetrance results in a significant physical, emotional and economic burden in HPAH families. Because 75% of subjects with HPAH have a New York Heart Association functional class rating of III or IV at the time of …