In the largest collaborative study so far, an international team of researchers from the European EuroEPINOMICS consortium, including scientists from VIB and Antwerp University identified novel causes for severe childhood epilepsies. The researchers analyzed the genetic information of 356 patients and their parents. In their analysis, the research teams looked for genes that had acquired new mutations in the children with severe epilepsies when compared to the DNA of the parents.  The results of the opensource study were published in the American Journal of Human Genetics.

In total, they identified 429 new mutations and in 12% of children, these mutations were considered unequivocally causative for the patient’s epilepsy. In addition to several known genes for childhood epilepsies, the research team found strong evidence for additional novel genes, many of which are involved in the function of the synapse, the main structure in the nervous system that allows for communication between neurons.

The most surprising finding in the current study is a gene called Dynamin 1. Dynamins are functionally associated with synapses, which are important for the communication between nerve cells. When the researchers looked on a network level, they found that many of the genes that were found to be mutated in patients had a clear connection with the function of the synapse.

These genes will hopefully tell the medical community a bit more about the underlying disease mechanisms and how they can be addressed with new treatments. The current study is the first time a significant proportion of genetic epilepsies can be explained through molecular findings. In the past, researchers have had to subject patients to a long diagnostic journey of various tests and investigations. With the novel technologies, researchers can now get the answer much faster, this will translate into better patient care.

Combining data sets of three large consortia has proven to be a productive and cost-effective strategy to unravel the molecular genetic background of severe epilepsies in childhood. Collaborations are definitively the way to tackle these individually rare disorders.

Epilepsies are amongst the most common disorders of the Central Nervous System (CNS), affecting up to 50 million patients worldwide. Up to one third of all epilepsies are resistant to treatment with antiepileptic medication and are associated with other disabilities such as intellectual impairment and autism. Severe epilepsies are particularly devastating in children.

In many patients with severe epilepsies, no cause for the seizures can be identified. There is increasing evidence that genetic factors may play a causal role in these epilepsies. The current study by three international consortia, including the NINDS-funded Epi4K and EPGP consortia and the ESF-funded European EuroEPINOMICS consortium, which includes researchers from more than 20 European countries, assessed the role of genetic factors in the largest group of patients with severe epilepsy identified so far.

Source:  VIB (the Flanders Institute for Biotechnology)