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Danish researchers have found a gene mutation leading to serious heart disease and sudden death

Researchers from Aarhus University Hospital and Aarhus University in Denmark have found a new gene mutation leading to serious hereditary heart disease and risk of sudden unexpected death. This gene has not previously been associated with heart disease and the finding offers new knowledge on why some develop dangerous cardiac arrhythmia risking sudden unexpected death.

Experimental analyses show that patients with this gene mutation have a defect in the transport of ions across cell membranes causing an increased pH value and reduced chloride concentration in the cells of the heart muscle. This leads to a shorter duration of what is called "the action potential". This means that the time during which the heart pumps out blood during a heart beat is reduced and the so-called QT-interval in the ECG is shorter causing the condition called short QT syndrome. It is a hereditary heart disease involving a huge risk of causing serious arrhythmia and death.

Through clinical and genetic data, researchers have identified two Danish families with abnormal ECGs and with a risk of sudden cardiac death. Several family members have experienced ventricular fibrillation – two have died of this and two have survived cardiac arrest. The two survivors are now treated with a special pacemaker, an implantable cardioverter defibrillation (ICD), which induces an electrical shock in case of arrhythmia. This makes the heart beat regularly again. As a consequence of this research, many other relatives with the same risk now receive preventive treatment with such an ICD.

 The scientific results have just been published in the internationally acknowledge scientific journal Nature Communications.


Zebra fish have been test animals

The results have been obtained through translational research where doctors and researchers have collaborated closely in recent years. Zebra fish, primarily known from the aquarium, have been used as a model organism. In the laboratory the fertilized eggs from the fish have been used, because they develop a heart beat after only 24 hours and after 48 hours blood circulation is developed. The advantage of using the "young" zebra fish is that they are transparent, i.e. the heart can be observed in the living fish through a microscope.

In zebra fish it is documented that the mutation in question actually causes disease. In physiological tests, researchers have found out that the patient's mutation leads to loss of ion transport across cell membranes.

- We have demonstrated that when we insert the mutation in the zebra fish, the ion transport in the fish heart stops and the fish develops the same problem as the patients, i.e. short QT syndrome, says Henrik Kjærulf Jensen, Associate Professor, Consultant, DMSci and PhD at Department of Cardiology, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University.


Huge perspectives  

There are huge perspectives in the current results opening the door to an entirely new field to be further investigated both clinically and experimentally.

- So far, "only" two families with this mutation have been identified, but the mutation may be far more frequent and we are ready to initiate a screening in a broader population both nationally and internationally, says Henrik Kjærulf Jensen.

The current results may already contribute to saving lives because the discovery of this gene initiates the testing of a number of genes with a similar function for mutations in other patients. If you have this mutation and thus a risk of serious arrhythmia and early death, an ICD is offered as a preventive and potentially life-saving treatment.


Behind the research result:

Type of study: Translational research

Collaborators: Department of Cardiology and Department of Molecular Medicine, Aarhus University Hospital. Department of Clinical Medicine, Department of Biomedicine and Department of Molecular Biology and Genetics, Aarhus University. Rigshospitalet (Copenhagen University Hospital), University of Copenhagen, University of Oslo and University of Lithuania.

External financing: None

Conflicts of interest: None

Link to the scientific article: ”Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome” in Nature Communications:


Further information:

Henrik Kjærulf Jensen, Consultant, Associate Professor, DMSci, PhD, Department of Cardiology, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University. Tel.: +45 7845 2033 Mobile phone: +45 4058 3417

E-mail: hkjensen@clin.au.dk


Christian Aalkjær, Professor, DMSci, Department of Biomedicine, Aarhus University.

Tel.: +45 3045 4306

E-mail: ca@biomed.au.dk