A consortium of researchers in Europe discovered a new gene involved in severe childhood epilepsy. The researchers found mutations in CHD2, a gene they now know is responsible for patients with Dravet syndrome, a form of epilepsy that is resistant to anti-epileptic drugs for most patients. This research also helped create a new model in using zebra fish in the process of finding new drugs to treat this form of epilepsy.
Approximately 80% of Dravet patients have a mutation in the gene known as SCN1A, however, there is no genetic cause for the rest of the 20% of patients. Onset of Dravet syndrome is during infancy, with fever often being the trigger for the first seizures. This form of epilepsy is considered pharmacoresistant, in other words, it cannot be treated with any current anti-epileptic drugs for most patients. The effects of Dravet syndrome ranges from moderate to severe, patients usually developing forms of autism or cognitive delays. Moreover, there is also an increase in risk of Sudden Unexplained Death In Epilepsy, also known as SUDEP. Overall, with limited treatment and the severity of the condition, individuals with Dravet syndrome experience a diminished quality of life.
The discovery on Jan. 22 was made possible through a consortium known as EuroEPINOMICS Rare Epilepsy Syndromes, which was funded €2,37 million in 2011 from national agencies concerned with searching for new genes for various seizure disorders. The research involved looking across the genome for errors in the DNA of patients copied from their parents egg or embryo, the resultant of them being the first in the family to develop Dravet syndrome.
Out of 9 patients, three of them were identified to have mutations in CHD2, short for chromodomain helicase DNA binding protein 2. Research was then confirmed on zebra fish larvae which has, over the last ten years, become a model for epilepsy study. Researchers rapidly generated this larvae with loss in the function of CHD2. Using technology similar to an EEG, the researchers detected epileptic seizures in the animals.
Peter De Jonghe who led the analysis said that not only did researchers discover a new gene for Dravet syndrome, but this also opens the door wide open for finding the genetic background of many disorders. Jonghe also notes how this was not feasible in the past because it took analyzing large families to understand the genetic background of this form of epilepsy, and many Dravet patients would not go on to have families due to their illness. The new technology bypasses looking at families – focusing on the egg and embryo of the parents of the Dravet syndrome patient.
Camila Esguerra who is head of the zebra fish research described this discovery of the gene as the next big step forward since they validated zebra fish as a model for epilepsy. She also says in the report that the methods are now well-established in their laboratory and the zebra fish models are now suited for screens – a profound progress in discovering new anti-epileptic drugs.
Julian Isla, executive director of the Dravet Syndrome Foundation-EU, adds to the report of how this discovery of the gene from this severe form of epilepsy most especially benefits the 20% of Dravet cases in which the responsible gene is still unknown. Now, these patients and most importantly, their families, will have answers to their genetic diagnosis.