Prof Jamie Vandenberg Victor Chang Institute

2019 SCD Research Update

Sudden Cardiac Arrest (SCD) Research Update

12 August 2019

The spectacular developments in sequencing the human genome has revolutionised heart research and led many to speculate that we will soon enter an era of personalised genome guided precision medicine. However, the speed with which we can now “read” the human genome far exceeds our capacity to interpret how gene mutations affect protein function and clinical outcomes. We urgently need to dramatically improve our skills at characterising how mutations affect gene outputs, i.e. functional genomics.

Mutations in the KCNH2 gene are a well-established cause of sudden cardiac arrest, caused by disturbed electrical signalling, in otherwise healthy young people. Yet, we now appreciate that the majority of variants identified in the KCNH2 gene do not change its function. The planned global efforts to sequence millions of genomes in the next few years will result in thousands of variants being identified in the KCNH2 gene; some of these will identify patients at increased risk of sudden arrest but most of these variants will be benign.

Dr Ashish Mehta Victor Chang Cardiac Research Institute

To cope with this deluge of variants of unknown significance we will develop a high throughput functional assay to assess how every possible mutation in KCNH2 affects the electrical function of heart cells. To achieve this, we will utilise state-of-the art robotic platforms to first help generate thousands of mutations in KCNH2 and then to assess the electrical consequences of these mutated genes. This data will be made available to geneticists, treating physicians and their patients through publicly accessible databases, such as ClinVar, so that all patients (both in NSW and throughout the world) who have their genome sequenced can access this data.

Successful completion of this project would pave the way for using a similar approach to tackle other genes associated with sudden cardiac death and ultimately any cardiac disorder where it is possible to develop a high throughput assay to quantify altered function. It will also help to establish the Victor Chang Cardiac Research Institute and NSW as a world centre for functional genomics for inherited heart diseases and for the clinical impact of our heart research.

*This project was supported by the NSW Government's Cardiovascular Research Capacity Building Program.

-- ENDS --

For all media enquiries and interview requests, please contact:

Julia Timms
Head, Media & Communications
0457 517 355

Acknowledgement of Country

The Victor Chang Cardiac Research Institute acknowledges the traditional custodians of the land, the Gadigal of the Eora nation, on which we meet, work, and discover.
Our Western Australian laboratories pay their respect to the Whadjuk Noongar who remain as the ongoing spiritual and cultural custodians of their land.