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Centenary Institute - Medical Research
Centenary Institute - Medical Research

Building the case for a closer look at known heart-disease genes

Centenary Institute scientists have conducted a study which could change how researchers discover the causes of genetic heart disease.

At the moment, the bulk of genetic testing focuses on the protein-coding sections of DNA to look for disease-causing variants. However, these protein-coding regions only make up about two-per-cent of our entire DNA sequence.

In a study published in scientific journal Circulation: Genomic and Precision Medicine, researchers in Centenary’s Molecular Cardiology Program screened 500 families affected by hypertrophic cardiomyopathy – a common genetic heart condition which occurs when the heart muscle thickens, making it difficult to pump blood.

The researchers focused on one of the main disease-causing genes, known as MYBPC3, and discovered they were able to attribute the cause of hypertrophic cardiomyopathy in four families to a variant found in the non-coding region of the DNA.

First-time Lead Author Emma Singer says while on the surface, it may appear to be a small breakthrough, it’s still important for patients affected by genetic heart disease.

“This study makes a major difference for those four families who otherwise would not have known the cause of their heart condition, which in some cases, can be fatal,” says Emma.

Senior Researcher Dr Richard Bagnall is hopeful the study will help re-direct the broader focus of genetic heart disease research.

“We would consider this a pilot study, so we are hoping our results will encourage other researchers to undertake a similar approach in larger cohorts of patients with other known disease-causing genes.

 “This study demonstrates why we need to be looking at the known genes more closely and more carefully – because we’re finding that we’re having a lot more success that way, rather than trying to find a new gene altogether that causes disease.”

Key value of RNA analysis of MYBPC3 splice site variants in hypertrophic cardiomyopathy has been published in the scientific journal Circulation: Genomic and Precision Medicine.

View the full media release as a PDF.

Learn more about Centenary’s Molecular Cardiology Program.

New insights into why young people die suddenly

A study led by scientists at the Centenary Institute could provide some families with a clearer insight into why a young loved one may have experienced an otherwise unexplained cardiac arrest and in some cases, sudden death.

Arrhythmic right ventricular cardiomyopathy (ARVC) is a poorly understood genetic cardiomyopathy. It occurs if the muscle tissue in the right side of the heart undergoes cell death and is replaced with fat and scar tissue; disrupting the heart’s electrical signals and causing an abnormal heart rhythm.

Researchers from the Centenary Institute, Royal Prince Alfred Hospital, Royal North Shore Hospital and the University of Sydney examined four families in which one family member (under the age of 30 years) had ARVC and experienced a cardiac arrest as a result. In two cases, the patients survived, while in the other two cases, the patients died suddenly.

Studies to date suggest patients must exhibit an obvious structural change to their heart before they are at risk of a sudden cardiac episode. This study shows for the first time that this isn’t always the case, with none of the four patients’ hearts exhibiting any structural changes. In all four cases however, a genetic error in a particular gene called PKP2 was identified.

“This study could force us to re-evaluate how we treat patients with this particular type of cardiomyopathy. For example, should we be more aggressive in treating these patients who carry the PKP2 gene error, but don’t show any clinical evidence of having this disease?” says Head of Centenary’s Molecular Cardiology Program, Professor Chris Semsarian AM.

“It also opens the door for potential gene-targeted therapy further down the track, with the aim of preventing patients with ARVC from experiencing a cardiac arrest.”

Lead author and Head of Centenary’s Clinical Cardiac Genetics Group within the Molecular Cardiology Program, Dr Jodie Ingles says the results may also help to provide closure for some families.

“In many cases of cardiac arrest or sudden death, it can be difficult to identify the precise cause, particularly if the patient’s heart does not show any structural changes. Now, we can attribute a specific gene as to why some people die suddenly, in cases that would otherwise go unexplained,” says Dr Ingles.

View the full media release as a PDF.

Read the paper published in Circulation: Genomic and Precision Medicine.

Learn more about Centenary’s other life-saving medical research breakthroughs.

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