According to a new study, published in the Journal of Neuroscience, a mutation in a gene called SCN1B, which has been linked to genetic epilepsy with febrile seizure plus (GEFS+), could ‘work’ by producing an abnormal protein that takes on an additional, harmful function. This knowledge could lead to the development of much-needed new therapies for GEFS+.The term ‘GEFS+’ describes families in which members from different generations have varying types of epileptic seizure, and even different epilepsy syndromes. Affected people nearly always have a history of febrile convulsions.During the study, researchers at the University of Michigan Medical School, led by Dr Lori Isom, bred rodents that carried one mutated copy of the SCN1B gene and one healthy copy. They then tested the seizure susceptibility of the animals in response to temperature (a model of high fever in children) and compared it to that of rodents with a) only one (healthy) copy of the SCN1B gene (as opposed to two) and b) two healthy copies of the gene (controls).The team noticed that the rodents with one mutated copy and one healthy copy of the SCN1B gene were more susceptible to seizures induced by high body temperature than those with one or two healthy copies of SCN1B. They concluded from this that the presence of one faulty copy of the gene was enough to make the mice more susceptible to seizures.On closer examination of the effects of the SCN1B mutation, the researchers found that the resulting abnormal protein didn’t interact in the usual way with other proteins, and that it was unable to generate the types of electrical signal needed for neurons to communicate properly. They also noticed that the faulty protein didn’t reach the correct location inside neurons, and the authors suggest that this could have a knock-on effect of preventing the normal form of the protein from reaching its intended location.Finally, the abnormal protein appeared to affect the way in which the neurons were able to attach to each other, thereby having a negative effect on their shape and function. According to the authors, this could be due to the faulty protein competing with the normal form to keep two adjacent cells together.These important insights will hopefully lead to the development of new therapies for GEFS+, which block the damaging effects of this abnormal protein.Nine different mutations in the SCN1B gene have been reported in people with epilepsy. The authors hope that animal models of each of these different mutations will be generated, so that we can better understand how they produce seizures.Author: Dr Özge ÖzkayaClick here for more articles about brain science including genetics.
ERUK Team2019-10-26T22:50:00+01:00June 16th, 2016|