An international team of researchers has pinpointed a genetic mutation that appears to be responsible for a rare condition that triggers seizures in babies. The mutation was identified thanks to new data science technologies that enabled the scientists to sift through extremely large sets of genetic information.
Infantile-onset epilepsy is a seizure disorder that appears in infants in their first year of life. The condition often occurs in clusters and infants can experience hundreds of spasms per day and can be followed by other types of seizures later in childhood.
Researchers at the University of Rochester School of Medicine and Dentistry, led by neurogeneticist Alex Paciorkowski, M.D., along with collaborators at Swansea University in the UK, and Seattle Children’s Hospital, obtained the full genetic profile of two individuals with the condition through a process called whole exome sequencing.
Using this data, the researchers searched for “misspellings” – or mutations – in the genetic code that may explain what is going on in the brains of infants with these seizures. The process, which Paciorkowski characterizes as akin of finding a needle in a haystack, was aided by access to supercomputing resources of the University of Rochester’s Center for Integrative Research Computing and the Health Sciences Center for Computational Innovation.
Using this computation power and a unique software program called SOLVE-Brain, which was developed by Dalia Ghoneim, a bioinformatician in Paciorkowski’s lab, the researchers were able to sift through these very large sets of data in a methodical manner.
The team identified a mutation found in a snippet of genetic code (TUBB2A) that is responsible for producing proteins called tubulins. These proteins play a critical role in the developing brain. Tubulins create the molecular scaffolding that helps neurons take shape, spread throughout the brain, and build communication networks with each other. In individuals with infantile-onset epilepsy, these genes do not function properly, which can stunt brain development and be one of the underlying causes of the seizures.
These findings – which appear in The American Journal of Human Genetics – will help researchers understand the mechanics of the disease and represent an important first step to developing potential new treatments.