Opposing Effects on Na_V1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures.

ABSTRACT:

Background

Variants in the SCN2A gene that disrupt the encoded neuronal sodium channel Na_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.

Result

SUBMITTER: Ben-Shalom R 

PROVIDER: S-EPMC5796785 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature