Opposing effects on NaV1. 2 function underlie differences between SCN2A variants observed in individuals with autism spectrum disorder or infantile seizures.

BACKGROUND:

Variants in the SCN2A gene that disrupt the encoded neuronal sodium channelNa_V1.2 are important risk factors for autism spectrum disorder (ASD), developmental delay, and infantile seizures. Variants observed in infantile seizures are predominantly missense, leading to a gain of function and increased neuronal excitability. How variants associated with ASD affect Na_V1.2 function and neuronal excitability are unclear.

METHODS:

We examined the properties of 11 ASD-associated SCN2A variants in heterologous expression systems using whole-cell voltage-clamp electrophysiology and immunohistochemistry. Resultant data were incorporated into computational models of developing and mature cortical pyramidal cells that express Na_V1.2.

Biological psychiatry 82.3 (2017): 224-232.
Ben-Shalom, Roy, et al.
https://www.sciencedirect.com/science/article/pii/S0006322317300410