A gene known to be essential in the formation of the interventricular septum and of the cardiac valves can be responsible for the development of the Brugada syndrome.
This is the main result of a study recently published in the journal Nature Genetics by the research group of Amsterdam cardiologist Connie R. Bezzina. The study also involved scientists at the Biocenter of the University of Würzburg: Professor Manfred Gessler, head of the Department for Developmental Biochemistry, and his team have been studying the respective gene, the Hey2 gene, for a long time.
Gessler and his associates identified the Hey2 gene more than ten years ago. In their studies, they were also able to show in an animal model that the gene plays a significant role in the formation of the interventricular septum and of the cardiac valves. "However, the fact that the gene is involved in the electrical activity of the cardiac muscle and conduction cells has not been shown before," says Gessler.
The Brugada syndrome
The Brugada syndrome has been recognized for only just about 20 years as a distinct genetic arrhythmia of the heart. It was first described in 1991 by two brothers, Josep and Pedro Brugada. Patients suffering from this disease are affected by an abnormal electrical conduction in the heart associated with a high risk of sudden cardiac death. They are subject to recurrent cardiac arrhythmias, which can lead to loss of consciousness. In the worst case, ventricular fibrillation occurs when the ventricles of the heart contract so rapidly that they cease to pump the blood effectively, which results in cardiovascular failure.
"Previously, it was known that about 20 percent of the patients have defects in the sodium ion channel of the cardiac cells, predominantly in the subunit encoded by the SNC5A gene. However, the causes of the disease remained unclear in the majority of cases," says Manfred Gessler.
In the search for further risk factors, the study group of Connie R. Bezzina first conducted genome-wide association studies, involving more than 1000 patients. As expected, they found that the disease is correlated with certain genetic variants of the SCN5A gene and of the related SCN10A gene, which both have a function in cardiac excitation propagation. The scientists confirmed this finding in further patient cohorts.
To the researchers’ surprise, however, the first analysis also revealed statistically significant data indicating that genetic variations near the HEY2 gene play a role in the development of the Brugada syndrome. These results were confirmed in additional patient cohorts as well.
Defects in the Hey2 gene identified
In a joint project with the Amsterdam study group, the Würzburg researchers then achieved a major breakthrough: "With the help of special optical methods, we were able to establish that mice lacking one of the two copies of the Hey2 gene also exhibit detectable changes to the ventricular excitation propagation and the subsequent repolarization of the cardiac muscle cells comparable to those of the Brugada syndrome," Gessler explains. Hence, the HEY2 gene, previously only linked to developmental defects of the heart, also seems to have an impact on the correct formation of the cardiac conduction system and the electrical excitability of the cardiac muscle cells.
Further studies are already in progress in order to shed more light on the molecular mechanisms of this defect.
Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death; Connie R Bezzina et al. Nature Genetics, published online 21 July 2013; doi:10.1038/ng.2712
Contact personProf. Dr. Manfred Gessler, T: +49 (0)931 31-84159,
Gunnar Bartsch | Uni Würzburg
Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania
The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction