Researchers have identified two new genes and implicated 25 distinct mutations in serious forms of epilepsy, suggesting a new direction for developing tailored treatments for the neurological disorders. The findings by an international research collaboration appear in the journal Nature.
The cause of epileptic encephalopathies is largely unknown; while genes are believed to play an important role, specific genes have been identified only in a small number of cases. Led by Daniel Lowenstein, MD, professor of neurology at the University of California, San Francisco, researchers gathered genetic information on 264 children with epileptic encephalopathies and their parents. They then focused on identifying all new mutations in the children using next-generation sequenced data. The Duke Center for Human Genome Variation conducted this analysis, and confirmed 329 de novo mutations.
Most of these mutations had no connection to the risk of disease, but the researchers showed that a fraction of them strongly influence risk. They saw that the genes already known to cause epileptic encephalopathies carried multiple de novo mutations. However, they found multiple de novo mutations in two additional genes—GABRB3 and ALG13—not previously connected to epileptic encephalopathies. Developing and applying new statistical approaches to determine risk factors, the researchers identified a statistical excess of mutations of those genes, and concluded that the two new genes were influencing epileptic encephalopathies. Combining the known genetic mutations with the newly identified genetic mutations, they have now pinpointed the genetic cause of more than 10% of epileptic encephalopathies. Read the article preview.
