Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Disease Gene for Early Infantile Epilepsy found

25.04.2014

A severe form of epilepsy in infants is caused by hitherto unknown mutations of the HCN1 ion channel. The changes in the genetic material are de novo mutations, i. e. they are not present in the parents. This is reported by a German-French research team in the journal “Nature Genetics”.

Epileptic encephalopathies are severe disorders which occur even in babies. They are accompanied by a disturbed maturation of the brain as well as by an impairment of the mental and sometimes also of the motoric development. Seizures typically appear first in combination with fever and cannot usually be treated.


Structure of the HCN1 channel in the cell membrane of nerve cells. The asterisks mark the spots where mutations were found that cause an early infantile epilepsy resembling the Dravet syndrome.

Picture: Institute for Human Genetics

Another form of early infantile epileptic encephalopathy, which has been known for some time, is the Dravet syndrome. It occurs in about one child out of 30,000 and is caused by mutations of the sodium channel gene SCN1A. However, many children suffering from a disorder resembling the Dravet syndrome have no mutations of SCNA1, so there must be other genes responsible for this early infantile type of epilepsy.

Mutations discovered in the HCN1 ion channel

In the search for new disease genes as the cause of early infantile epileptic encephalopathies, scientists from Paris and Würzburg have now made a discovery. In the genetic material of nearly 200 affected children, where mutations of the SCNA1 gene had already been ruled out, they discovered in six cases the pathogenic mutations in another ion channel gene, namely HCN1. These dominant mutations arise spontaneously during the generation of the parents' reproductive cells; they are not present in the parents' body cells.

“The electric current carried by the HCN1 cation channel is also referred to as 'pacemaker', because it stimulates rhythmic activity in spontaneously active nerve cells”, says Professor Thomas Haaf, head of the Institute for Human Genetics of the University of Würzburg Animal models had already suggested that this channel has a key role in epileptic disorders. “But so far no corresponding mutations had been found in patients.”

Differences from the Dravet syndrome

At the beginning the seizures of children with mutations of the HCN1 gene are hardly distinguishable from the Dravet syndrome, but at later stages they are: “There is an increased occurrence of atypical seizures. All affected children have an impairment of intelligence and behavioural disorders, including autistic behaviour”, says Professor Haaf.

The study was led by Dr. Christel Depienne, who worked for two years until the end of 2013 as a visiting scientist at the Würzburg Institute for Human Genetics. From there she coordinated the German-French research team.

Consequences of the new discovery

How can patients benefit from the new findings? This is not an easy question to answer, because it is usually a long way from the discovery of a pathogenic gene mutation to the therapy.

Professor Haaf comments: “In any case, a better understanding of the molecular causes of the disorder will be helpful in the development of new therapeutic approaches, for example of drugs with a specific effect on the HCN1 currents. The results enable us already to make a correct diagnosis of this very severe early infantile disorder, which usually occurs sporadically, and to provide genetic counselling to parents with regard to their further family planning.”

“De novo mutations in HCN1 cause early infantile epileptic encephalopathy”, C. Nava, C. Dalle, A. Rastetter, …, T. Haaf, E. Leguern, C. Depienne, Nature Genetics, published online on 20 April 2014, doi:10.1038/ng.2952

Contact

Prof. Dr. Thomas Haaf, Institute for Human Genetics of the University of Würzburg, T (0931) 31-88738, thomas.haaf@uni-wuerzburg.de

Robert Emmerich | idw - Informationsdienst Wissenschaft
Further information:
http://www.uni-wuerzburg.de

More articles from Life Sciences:

nachricht Research team creates new possibilities for medicine and materials sciences
22.01.2018 | Humboldt-Universität zu Berlin

nachricht Saarland University bioinformaticians compute gene sequences inherited from each parent
22.01.2018 | Universität des Saarlandes

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Thanks for the memory: NIST takes a deep look at memristors

22.01.2018 | Materials Sciences

Radioactivity from oil and gas wastewater persists in Pennsylvania stream sediments

22.01.2018 | Earth Sciences

Saarland University bioinformaticians compute gene sequences inherited from each parent

22.01.2018 | Life Sciences

VideoLinks Wissenschaft & Forschung
Overview of more VideoLinks >>>