Characterization of a de novo SCN8A mutation in a patient with epileptic encephalopathy.

ABSTRACT:

Objective

Recently, de novo SCN8A missense mutations have been identified as a rare dominant cause of epileptic encephalopathies (EIEE13). Functional studies on the first described case demonstrated gain-of-function effects of the mutation. We describe a novel de novo mutation of SCN8A in a patient with epileptic encephalopathy, and functional characterization of the mutant protein.

Design

Whole exome sequencing was used to discover the variant. We generated a mutant cDNA, transfected HEK293 cells, and performed Western blotting to assess protein stability. To study channel functional properties, patch-clamp experiments were carried out in transfected neuronal ND7/23 cells.

Results

The proband exhibited seizure onset at 6 months of age, diffuse brain atrophy, and more

SUBMITTER: de Kovel CG 

PROVIDER: S-EPMC4490185 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature