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
Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Life Sciences
27.04.2017 | Physics and Astronomy
27.04.2017 | Earth Sciences