Genetic testing solves mystery of teens’ sudden deaths

A New Zealand family and two Australian families, who lost young people to sudden cardiac death, finally have answers thanks to contemporary genetic testing.

Up to 90 unexplained sudden cardiac deaths are reported per year in Aotearoa New Zealand in people under 40 and in around a third of cases, no cause has been found.

“This new finding has been made possible by the technology we have available now,” says lead researcher Dr Polona Le Quesne Stabej from Waipapa Taumata Rau, University of Auckland.

“In 2001, an international consortium of scientists sequenced the entire human genome at a cost of more than two billion dollars. Now the University can sequence an entire genome for between one and three-thousand dollars.”

The family, who have asked for privacy, had earlier agreed to standard genetic testing, but that failed to find a cause.

They have been supported from early on by clinicians from the national Cardiac Inherited Diseases Group (CIDG), which was founded in 2000 by Professor Jon Skinner to coordinate care for whānau.

Skinner says it was heartbreaking to be caring for the family and terrible to not understand what was going on. This discovery will bring relief to the families and clinicians who will have information to prevent further deaths.

“Parents who have lost a child often carry an irrational sense of guilt, and it has been a powerful motivator for me and the team when a parent says, ‘Thank you doctor, I don’t have to blame myself any more.’”

The value of this sort of research is it immediately translates into improved care for impacted families, Skinner says.

In 2024, the family agreed to participate in the new research project led by Pūtahi Manawa, a centre of excellence for heart research at the University. See European Heart Journal.

The research team made the discovery using long-read DNA sequencing, an advanced technique capable of analysing large, complex regions of the genome.

By applying long-read sequencing to historical DNA samples, the researchers were able to identify genetic changes that had previously gone unnoticed.

The whole genome testing results were analysed by bioinformatician Dr Zoe Ward, who discovered the genetic abnormality, called a ‘repeat expansion’, in the DMPK gene.

These repeat expansions can be difficult to detect using standard genetic testing.

This genetic abnormality is known to cause myotonic dystrophy type 1, an inherited condition that leads to muscle weakness and other symptoms, including sometimes affecting the heart.

“Our findings suggest this genetic change may be an overlooked cause of sudden cardiac death in young people, especially when standard tests find no answer, and we recommend checking for this DMPK repeat in unexplained cases,” says Le Quesne.

The University’s $11 million Precision Medicine Initiative supports this and related research with funding and advice.

Researcher Professor Cris Print, who works with the initiative, says new long-read genome sequencing has allowed scientists to understand the biology of sudden cardiac death much better.

“This increase in biological understanding, allows clinical practice to change and saves lives,” Print says.

The New Zealand research was confirmed by Associate Professor Richard Bagnall, a leading expert in inherited heart diseases, at the Centenary Institute in Australia.

Bagnall identified the same genetic expansions in several young people who died suddenly of cardiac causes.

All this makes a strong case for including DMPK in any genetic screening for sudden cardiac death, the authors say.

Data sovereignty important for Māori

A Māori advisory group, or Kaitiaki Rōpu, has steered the project to ensure it is culturally safe for participants, as the family at the centre is Māori.

The rōpu ensures whānau consent to DNA being used and have input to how it is disposed of after the genetic testing, including use of specific karakia.

“DNA is one of the most taonga substances – everything about us, about our whakapapa is in our DNA,” says Saraya Hogan (Ngāti Hako), a rōpu member who is a genetic counsellor and medical laboratory scientist who worked on the project.

Print says working with the Kaitiaki Rōpu improves data governance for all New Zealanders. “We learn from Māori how to do this really well.”

Pūtahi Manawa is a large collaborative research centre focused on closing the gap in heart health for Māori and Pacific People in Aotearoa New Zealand.

Read about the University of Auckland’s Precision Medicine Initiative