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.
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
Prof. Dr. Thomas Haaf, Institute for Human Genetics of the University of Würzburg, T (0931) 31-88738, email@example.com
Robert Emmerich | idw - Informationsdienst Wissenschaft
A cell senses its own curves: New research from the MBL Whitman Center
29.04.2016 | Marine Biological Laboratory
A New Discovery in the Fight against Cancer: Tumor Cells Switch to a Different Mode
29.04.2016 | Universität Basel
Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.
Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...
Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.
In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...
Honeycomb structures as the basic building block for industrial applications presented using holo pyramid
Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...
Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences (CAS). This work is about avoiding costly and unstable fullerenes.
Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences...
As one of the leading R&D partners in the development of surface technologies and organic electronics, the Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP will be exhibiting its recent achievements in vacuum coating of ultra-thin glass at SVC TechCon 2016 (Booth 846), taking place in Indianapolis / USA from May 9 – 13.
Fraunhofer FEP is an experienced partner for technological developments, known for testing the limits of new materials and for optimization of those materials...
27.04.2016 | Event News
15.04.2016 | Event News
12.04.2016 | Event News
29.04.2016 | Physics and Astronomy
29.04.2016 | Health and Medicine
29.04.2016 | Life Sciences