Inherited cardiovascular diseases will be put under the spotlight in the Garvan Institute of Medical Research’s new Elusive Hearts Study, thanks to support from the Medical Research Future Fund’s Cardiovascular Health Mission.
Over the next three years, the aim of the gene discovery research program is to pinpoint the causes of rare cardiac diseases that present in childhood and early adulthood and increase the success rate of genetic testing, providing families with essential knowledge to inform their screening and treatment options.
The researchers will screen for conditions including arrhythmia syndromes, such as catecholaminergic polymorphic ventricular cardiomyopathy (CPVT), a heart rhythm disorder that increases the chances of cardiac arrest with stress or exercise; as well as inherited cardiomyopathies and other cardiac disorders that appear to run in families.
“In my role as a cardiac genetic counsellor, I spend a lot of time supporting young families to go through the process of genetic testing for heart conditions that might be inherited,” says Associate Professor Jodie Ingles, leader of the Elusive Hearts Study, Co-Lead of the Rare Disease Program and Head of the Clinical Genomics Lab at Garvan.
“The diagnostic pickup rate for genetic testing has remained fairly constant at only around 40% for the last decade. That means in many cases we can’t find a diagnosis to explain the cause of the inherited condition, and we can’t then offer more certainty to relatives with cascade genetic testing to see if they, too, have inherited the genetic condition. This can be concerning for the family, as it makes it harder to predict disease risk in the future and to know whether they need to keep getting check-ups with their cardiologist.”
The researchers will partner with networks throughout Australia to recruit more than 200 individuals who have undergone genetic testing for an inherited cardiac condition. They will focus on families with the greatest likelihood of having an inherited condition, such as those with a family history of cardiac disease, early onset of symptoms and severe presentation. The families involved will undergo more comprehensive sequencing and genomic analysis, drawing on the expertise of the Garvan Rare Disease Program.
The study will also help to describe the clinical characteristics of atypical presentations of heart disease, contributing to more broadly applicable diagnostic frameworks.
“At this point clinical genetic testing isn’t very equitable – if you’re a European family, the chance of identifying the cause of the disease is much higher than for families with diverse ancestry groups, where we are much more likely to have uncertain genetic findings,” says Associate Professor Ingles.
“We will focus on identifying the underlying genetic cause of disease in those families who have exhausted all clinical genetic testing pathways, including those from more diverse ancestry groups who otherwise would miss out on the benefits of a genetic diagnosis.”
The Elusive Hearts Study will be carried out in collaboration with the Centre for Population Genomics, HeartKids Ltd and Australian Genomics. It will be recruiting in coming months. For more information, contact firstname.lastname@example.org or +612 9359 8049.
Addressing unsolved challenges in genetic disease diagnosis, clinical RNA sequencing and cancer surveillance
The Medical Research Future Fund has also awarded a grant to Dr Ira Deveson, Head of Garvan’s Genomic Technologies Group, to explore how nanopore sequencing can streamline and improve the diagnosis of human diseases.
Nanopore sequencing is an emerging DNA/RNA sequencing technology that is reshaping the genomic medicine landscape: it is faster, cheaper and more portable and has many other advantages over traditional sequencing methods.
As part of the Early to Mid-Career Researchers program, Dr Deveson’s two-year project will explore new ways of using nanopore sequencing and new bioinformatics approaches to address significant challenges in the genetic diagnosis of diseases, from rare inherited disorders to cancer.
“There are countless opportunities to streamline, improve and reimagine how we use nanopore sequencing in diagnosis,” Dr Deveson says. “This grant will allow us to develop new diagnostic tests and the pathways to implement them in the clinic. For patients with complex or undiagnosed diseases, these approaches could provide life-changing diagnostic clarity.”
If successful, Dr Deveson’s research could lead to wider adoption of nanopore sequencing in clinical settings. The findings could also pave the way for more accurate and timely diagnosis of diseases, improved treatment decisions, and better outcomes for patients.
Dr Ira Deveson is a Conjoint Lecturer at UNSW. Associate Professor Jodie Ingles is a Cardiac Genetic Counsellor at RPA Hospital and a Conjoint Associate Professor at St Vincent's Clinical School, UNSW Medicine and Health.