Media release
17 July 2008
Preventing sudden death in the young
University of Auckland researchers have established a new way to identify gene mutations, which will directly lead to
improved diagnosis of those at risk of sudden cardiac death.
Currently available genetic screening tests for long QT syndrome (LQTS) miss about a third of cases. Researchers at The
University of Auckland's Faculty of Medical and Health Sciences have recently made an important discovery which will
significantly increase the diagnostic hit rate.
Genetic diagnoses are important in LQTS because they identify the type of LQTS which guides treatment, and because they
permit accurate family screening and genetic counselling. Carey-Anne Eddy, the PhD researcher involved in the project,
working with Associate Professor Andrew Shelling said, "Current molecular genetic screening programs identify the
genetic cause in only about 70% of cases. This new test offers a dramatically improved success."
Long QT syndrome is an inherited disorder occurring in about 1 in 2000 people in New Zealand, which causes recurrent
collapse and sudden death. It is the leading cause of sudden unexpected death in young people.
"The risk of sudden death from LQTS can be significantly reduced with the correct medication and clinical treatment,"
says paediatric cardiologist Associate Professor Jon Skinner of Starship Children's Hospital. "However, the type of
genetic mutation and gene in which it occurs, directly influences the type of treatment to which each patient will best
respond. Knowing the genetic cause of LQTS in a family also allows extended family members to be screened and offered
the most suitable life-preserving treatment and, therefore, has extreme clinical value."
As part of a significant research endeavour to prevent sudden cardiac death in young New Zealanders, funded by Cure
Kids, the research study analysed the DNA of 26 patients with LQTS identified by the Cardiac Inherited Disease Group
(www.cidg.org) who had tested negative for LQTS gene mutations. The investigation, using new technology, revealed three
patients (11%), carried mutations responsible for LQTS which the conventional genetic tests could not detect.
The current standard genetic screening tests (called polymerase chain reaction, followed by genomic sequencing) can
detect small changes in a person's DNA. However, it can miss big deletions or large rearrangements of DNA. For this
reason, the researchers used a recently described genetic screening method which picks up large-scale gene changes,
known as multiplex ligation-dependent probe amplification (MLPA). The study identified two large deletions and one large
duplication in genes that encode potassium ion channels in the heart. With certain triggers, like exercise or emotional
stress, these mutations may cause an otherwise structurally-normal heart to undergo rhythmic changes which may lead to
fainting, epileptic-like seizures and even sudden death.
The research represents one of the biggest advances in the field since the discovery of the first three long QT genes
over ten years ago, and will change the routine testing of this important disease. It is published in the September
issue of Heart Rhythm.
ends