Identification of rare sequence variation underlying heritable pulmonary arterial hypertension
Publication: Nature Communications
Stefan Gräf, Matthias Haimel, Marta Bleda, Charaka Hadinnapola, Laura Southgate, Wei Li, Joshua Hodgson, Bin Liu, Richard M. Salmon, Mark Southwood, Rajiv D. Machado, Jennifer M. Martin,
Carmen M. Treacy, Katherine Yates, Louise C. Daugherty, Olga Shamardina, Deborah Whitehorn, Simon Holden, Micheala Aldred, Harm J. Bogaard, Colin Church, Gerry Coghlan, Robin Condliffe, Paul A. Corris, Cesare Danesino, Mélanie Eyries, Henning Gall, Stefano Ghio, Hossein-Ardeschir Ghofrani, J. Simon R. Gibbs, Barbara Girerd, Arjan C. Houweling, Luke Howard, Marc Humbert, David G. Kiely, Gabor Kovacs, Robert V. MacKenzie Ross, Shahin Moledina, David Montani, Michael Newnham, Andrea Olschewski, Horst Olschewski, Andrew J. Peacock, Joanna Pepke-Zaba, Inga Prokopenko, Christopher J. Rhodes, Laura Scelsi, Werner Seeger, Florent Soubrier, Dan F. Stein, Jay Suntharalingam, Emilia M. Swietlik, Mark R. Toshner, David A. van Heel, Anton Vonk Noordegraaf, Quinten Waisfisz, John Wharton, Stephen J. Wort, Willem H. Ouwehand, Nicole Soranzo, Allan Lawrie, Paul D. Upton, Martin R. Wilkins, Richard C. Trembath & Nicholas W. Morrell
12 April 2018
Summary:
Pulmonary Arterial Hypertension (PAH) is a fatal lung disease and causes the walls of the arteries become thick and stiff, narrowing the space for blood to pass through and increasing blood pressure then leading to heart failure.
The disease kills 50% of those affected within five years, but little was known about what caused the condition in some people. Now experts say they have discovered five genes that cause the illness and could pave the way for more treatments.
Scientists carried out the largest ever genetic study of the disease by analysing the genomes – the unique sequence of a person’s DNA – of more than 1,000 PAH patients for whom the cause of the illness was unknown.
They found that mutations in five genes were responsible for causing the illness in these people, including in four genes that were not previously known to be involved in the disease. In people with the condition these genes fail to effectively produce the proteins that are required for the structure, function and regulation of the body’s tissues, researchers found.