De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy.

ABSTRACT:

Background

Mutations of SCN8A encoding the neuronal voltage-gated sodium channel NaV1.6 are associated with early-infantile epileptic encephalopathy type 13 (EIEE13) and intellectual disability. Using clinical exome sequencing, we have detected three novel de novo SCN8A mutations in patients with intellectual disabilities, and variable clinical features including seizures in two patients. To determine the causality of these SCN8A mutations in the disease of those three patients, we aimed to study the (dys)function of the mutant sodium channels.

Methods

The functional consequences of the three SCN8A mutations were assessed using electrophysiological analyses in transfected cells. Genotype-phenotype correlations of these and other cases were related to the functional analyses.

SUBMITTER: Blanchard MG 

PROVIDER: S-EPMC4413743 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature