Landmark study uses whole genome sequencing to identify the genetic causes of hypertrophic cardiomyopathy.
Researchers at Royal Prince Alfred Hospital have used whole genome sequencing to more accurately diagnose the genetic causes of the potentially fatal heart condition hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease with a prevalence of up to one in 200 people. It affects both men and women at any age and occurs when the heart muscle thickens, making it difficult for the heart to pump blood. It can cause chest pain, shortness of breath, dizziness, fainting episodes or palpitation and in some cases, it causes sudden cardiac death.
Working in collaboration with Sydney Research partner the Centenary Institute and the University of Sydney’s Medical School, RPA researchers used whole genome sequencing to determine the complete DNA sequence of more than 70 people who are directly affected by the disease.
They identified a genetic cause of HCM in 20 per cent of families for which prior targeted genetic testing was inconclusive.
In families that had never had genetic testing, whole genome sequencing identified a diagnosis in 42 per cent of cases.
RPA cardiologist Professor Chris Semsarian AM said these findings translate to more accurate diagnosis and management of HCM in families.
“This is precision medicine - finding the exact genetic change which is leading to disease in individual patients,” Professor Semsarian said.
“The next step is to link those genetic changes with the clinical features of these patients.”
Using whole genome sequencing allowed the scientists to look at regions of patients’ genes which were previously not considered important. They found changes in introns (previously referred to as “junk DNA”) resulted in changes to the heart muscle, and could lead to disease.
The scientists also discovered how changes to mitochondria, often referred to as the powerhouse of a cell, generated similar changes to the heart muscle.
The study is published in world-leading scientific journal TheJournalof the AmericanCollegeofCardiology.
Lead author and Senior Researcher for the Centenary Institute’s Molecular Cardiology Program, Dr Richard Bagnall, believes it’s a game-changer in the field.
“This study shows we can use this incredible technology to diagnose hypertrophic cardiomyopathy in 2-out-of-10 more families,” Dr Bagnall said.
“But there is a lot more information within those whole genomes we haven’t even had a look at yet, so this is really just scraping the surface of what’s possible,” Dr Bagnall said.
Professor Semsarian, an internationally-renowned cardiologist with a specific research focus in the genetic basis of cardiovascular disease, said the trial showed whole genome sequencing was a useful first-line genetic test.
While whole genome sequencing data are larger and take longer to analyse than exome (targeted) sequencing - posing some challenges for incorporating it into clinical care - it has the potential to identify variants that no other technology can currently do in a cost-effective way.
He said the study will reduce the number of cases that are misdiagnosed as HCM and facilitate more targeted therapies with the ultimate goal to improve clinical management.