A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Winter, 2017 | Number 1, Volume 31

Defects in single gene lead to autism or infantile seizures

Researchers say that defects in a single gene can lead to either autism or infantile epilepsy, depending on whether the defects increase or decrease the effects of the gene. 

The gene, SCN2A, encodes a sodium channel protein called NaV1.2, which plays a critical role in allowing neurons to communicate electrically. Previous research showed that the SCN2A variants seen in infantile seizures lead to increased neuronal excitability, and the new study sought to discover the effects of the variants associated with autism. 

Roy Ben-Shalom and colleagues investigated 12 SCN2A mutations associated with autism to see how they affected the electrical properties of NaV1.2 channels in cultured human cells. They found that all 12 reduced the function of the sodium channel, but in different ways. The effects ranged from preventing the channel from forming at all to blocking the pore through which sodium needs to flow for the channel to function. Using computer modeling, the researchers determined that unlike the mutations seen in individuals with infantile seizures, the mutations associated with autism made it more difficult for the modeled neurons to send electrical signals. 

Ben-Shalom says, “It was remarkable to see how consistently neuronal function was disrupted by these different mutations seen in patients with autism. The mutations all affected the channel in slightly different ways, but they ended up affecting neurons in almost exactly the same way.” 

The researchers’ computer simulations also indicated that the mutations associated with autism would only have a major impact on the brain during development, because the neurons transition away from relying on NaV1.2 channels as they mature. They say this is consistent with the idea that autism begins prenatally or before one year of age. 

Study coauthor Kevin Bender says, “These findings solidify SCN2A’s status as one of the most important genes in autism.” He and his colleagues next plan to investigate whether the severity of autism can be predicted by a child’s specific SCN2A mutation.


“Opposing effects on NaV1.2 function underlie differences between SCN2A variants observed in individuals with autism spectrum disorder or infantile seizures,” Roy Ben-Shalom, Caroline M. Keeshen, Kiara N. Berrios, Joon Y. An, Stephan J. Sanders, and Kevin J. Bender, Biological Psychiatry, January 2017 (open access). Address: Kevin Bender, [email protected]


“Autism researchers discover genetic ‘Rosetta Stone,’” Nicholas Weiler, UCSF News, January 26, 2017.