Genetic Testing Solves Mystery Of Teenagers’ Sudden Deaths

The discovery of a genetic cause for young people’s
sudden cardiac deaths discovery will bring relief to the
families and clinicians who will have information to prevent
further 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 whānau 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 type1, 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 Australian 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 New Zealand 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

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