The most important basic question we need to answer is how the mutations that cause epilepsy and SID actually affect the eEF1A2 protein. Each of the individuals we know of with eEF1A2 syndrome has one mutant copy of eEF1A2 and one normal copy; we usually think of genetic disorders as having been inherited from one or both parents, but in these cases the mutation has occurred spontaneously. You can find some excellent background information on the way gene mutations can cause disorders of the brain at the Genes to Cognition website.

Do the mutations cause disease because there is no longer enough normal eEF1A2 protein to do its job properly? Alternatively, the mutant form of the protein could take on new properties- perhaps it binds to proteins it shouldn’t, or even interferes with the function of the normal eEF1A2 protein made by the other chromosome.

We need to know this before we can consider what kinds of therapies could be developed. If the problem is not enough eEF1A2, then we need to find ways to upregulate eEF1A2 in the brain (or replace it using gene therapy). If, though, the mutant protein is actually damaging the cells in which it’s expressed, then upregulating it would not be helpful. If this is the case, we need to find ways of switching off the mutant protein whilst still leaving the normal copy to do its job. We are making model systems with the mutations in order to start answering these questions.