Mutations in a gene called SCN2A can cause either infantile epilepsy or autism spectrum disorder (ASD) according to a new study published in the journal Biological Psychiatry.SCN2A is responsible for making a protein called NaV1.2 in the brain. NaV1.2 determines the electrical properties of neurons and their ability to communicate with each other, especially during early brain development. Mutations in SCN2A that cause a reduction in NaV1.2 activity lead to ASD, whereas mutations that cause increased activity of NaV1.2 lead to epilepsy.In a press release, one of the senior authors of the study Dr Stephan Sanders said: “The genetics of neuropsychiatric disease is often complicated, but here we have a single gene in which specific mutations can cause either infantile seizures or autism in a consistent and predictable manner. This gives us an opportunity to understand both what these disorders have in common and what makes them different.”In this study, the researchers from the University of California San Francisco, Lawrence Berkley National Laboratory and the University of Puerto Rico, analysed 11 different mutations in the SCN2A gene that were originally discovered in children with ASD. The team studied how those mutations affected the function of NaV1.2 in human cells grown in the laboratory.They saw that all mutations reduced the activity of the protein, but depending on their location on the gene, they either inhibited the production of the protein or blocked its function. The researchers then used these data to develop computer models predicting how these mutations, together with those that had previously been reported to cause infantile seizures, would affect the behaviour of nerve cells, especially during development.They found that while the mutations seen in children with infantile seizures made the neurons more excitable, those seen in children with ASD made them “unwilling” to send electrical signals.The lead author of the study, Dr Roy Ben-Shalom said: “It was remarkable to see how consistently neuronal function was disrupted by these different mutations [which] all affected the [protein] in slightly different ways, but they ended up affecting neurons in almost exactly the same way.”According to the authors, these findings are a first step toward understanding how different subtle changes in neuronal function inside the mother’s womb might lead to the development of either a seizure-prone brain or an autism-prone brain in infancy.Author: Dr Özge ÖzkayaClick here for more articles about brain science including genetics.
February 2nd, 2017|