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

OBJECTIVE: missense mutations in 2 children with intellectual disability and developmental delay but no seizures. METHODS: 1.6 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: 1.6 protein was reduced by the Glu1218Lys substitution. CONCLUSIONS: should be considered as a candidate gene for intellectual disability, regardless of seizure status.