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Rare sequence variants underlie heritable pulmonary hypertension

last modified Apr 13, 2018 05:38 PM

Dr Stefan Gräf, Prof Nick Morrell, and collaborators have identified four new genes involved in the development of pulmonary arterial hypertension (PAH).

PAH is a rare disorder caused by a narrowing of the blood vessels that lead from the heart to the lungs. As these arteries narrow, it becomes harder for the heart to pump blood through to the lungs, leading to breathlessness and heart failure. PAH affects around 1,200 people in the UK, mostly women in their 30s although it can affect people of any age. Current therapies may ease symptoms but there are no medical treatments available to cure the disease.

The study, published in Nature Communications, included more than 1,000 patients and around 6,500 controls. Sequence analysis revealed significant over-representation of rare variants in ATP13A3, AQP1 and SOX17, and provided independent validation of a critical role for GDF2 in PAH. In addition, the study has identified pathogenic mutations in the majority of previously reported PAH genes and provides evidence for the potential involvement of further genes.

Given the relatively young average age of diagnosis and the high mortality rate associated with PAH, it has a devastating impact on both sufferers and their families. Taken together, the new findings have provided insights into the molecular basis of PAH and indicate unexplored pathways for therapeutic intervention. 

Funding information: This study was funded by the National Institute for Health Research, British Heart Foundation, UK Medical Research Council, the Dinosaur Trust, and the UK NIHR Cambridge Biomedical Research Centre. Funding for the whole-exome sequencing was provided through a Bart's Charity award.

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