Dominant KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy.

ABSTRACT:

Objective

To identify the genetic basis of a family segregating episodic ataxia, infantile seizures, and heterogeneous epilepsies and to study the phenotypic spectrum of KCNA2 mutations.

Methods

A family with 7 affected individuals over 3 generations underwent detailed phenotyping. Whole genome sequencing was performed on a mildly affected grandmother and her grandson with epileptic encephalopathy (EE). Segregating variants were filtered and prioritized based on functional annotations. The effects of the mutation on channel function were analyzed in vitro by voltage clamp assay and in silico by molecular modeling. KCNA2 was sequenced in 35 probands with heterogeneous phenotypes.

Results

The 7 family members had episodic ataxia (5), self-limited infantile seizures (5),

SUBMITTER: Corbett MA 

PROVIDER: S-EPMC5109949 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature