Loss-of-function variants of SCN8A in intellectual disability without seizures.

ABSTRACT:

Objective

To determine the functional effect of SCN8A missense mutations in 2 children with intellectual disability and developmental delay but no seizures.

Methods

Genomic DNA was analyzed by next-generation sequencing. SCN8A variants were introduced into the Na_v1.6 complementary DNA by site-directed mutagenesis. Channel activity was measured electrophysiologically in transfected ND7/23 cells. The stability of the mutant channels was assessed by Western blot.

Results

Both children were heterozygous for novel missense variants that altered conserved residues in transmembrane segments of Na_v1.6, p.Gly964Arg in D2S6 and p.Glu1218Lys in D3S1. Both altered amino acids are evolutionarily conserved in vertebrate and invertebrate channels

SUBMITTER: Wagnon JL 

PROVIDER: S-EPMC5499976 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature