New gene discoveries improve diagnosis of inherited heart disease

Inherited heart conditions affect more than one in every 200 Australians and are a major cause of illness and premature death.

The study, published in Genetics in Medicine, re-examined data from the Australian Genomics Cardiovascular Disorders Flagship, a national program that originally sequenced the genetic material of more than 500 Australians living with cardiomyopathy (heart muscle disease) or primary arrhythmia syndromes (abnormal heart rhythms).

The research team applied updated analysis methods, examined a broader range of heart-related genes and ran advanced laboratory tests to check the impact of uncertain DNA variations in the genomic dataset. With this deeper investigation, they were able to give an extra 4% of participants a confirmed genetic diagnosis that earlier testing had missed.

“Each additional diagnosis has a direct and tangible impact,” said Associate Professor Richard Bagnall, Head of the Centre for Cardiovascular Research at the Centenary Institute and senior author of the study.

“It explains why a person developed heart disease, informs their treatment and can guide genetic screening for relatives who may also be at risk.”

The study also confirmed a new disease-causing gene (TBX20) for cardiomyopathy that had previously been omitted in standard testing.

“These results show us that the genetic basis of heart disease is broader and more complex than we once thought,” said Yuchen Chang, PhD candidate at the University of Sydney and the Centenary Institute, and first author of the study.

“By continually updating gene panels (checklists of genes linked to specific heart conditions) and validating uncertain results in the laboratory, we can improve diagnosis rates and deepen our understanding of these conditions.”

The researchers say that re-analysing genomic data with the latest tools and knowledge will continue to improve genetic diagnosis for inherited heart conditions. This means more families can receive timely answers, clinicians can tailor care more effectively and new discoveries can be more quickly put into practice to benefit patients.