Enhanced slow inactivation contributes to dysfunction of a recurrent SCN2A mutation associated with developmental and epileptic encephalopathy.

ABSTRACT:

Key points

The recurrent SCN2A mutation R853Q is associated with developmental and epileptic encephalopathy with typical onset after the first months of life. Heterologously expressed R853Q channels exhibit an overall loss-of-function as a result of multiple defects in time- and voltage-dependent channel properties. A previously unrecognized enhancement of slow inactivation is conferred by the R853Q mutation and is a major driver of loss-of-function. Enhanced slow inactivation is potentiated in the canonical splice isoform of the channel and this may explain the later onset of symptoms associated with R853Q.

Abstract

Mutations in voltage gated sodium (Na_V ) channel genes, including SCN2A (encoding Na_V 1.2), are associated with diverse neurodevelopmental

SUBMITTER: Ganguly S 

PROVIDER: S-EPMC8446326 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature