Understanding the mechanism and pathological consequences of mutations on the developmentally regulated SCN8A alternative splicing of exon 5.

Changes in the DNA sequence (mutations) of the SCN8A gene affect a sodium channel in the brain called Nav 1.6. This can cause a range of neurological conditions, such as epilepsy, developmental delays, cognitive impairment, autism spectrum disorder, and movement disorders. As the brain develops, using a mechanism called alternative splicing, the way the gene, SCN8A,  produces a key part of the sodium channel changes.  Mutations can affect this alteration or indeed may affect the channel differently depending on what alteration is present. This might explain why people with the same gene mutation can have different symptoms. The study aims to understand the factors that control this process and how specific mutations impact the function of the sodium channel.

By investigating the genetic and molecular factors involved, we hope to identify potential therapeutic strategies for treating these neurological conditions, particularly epilepsy. The idea is to eventually manipulate the way the gene produces different forms of the sodium channel at different stages of development to improve outcomes for affected individuals.