Gain-of-function FHF1 mutation causes early-onset epileptic encephalopathy with cerebellar atrophy.

ABSTRACT:

Objective

Voltage-gated sodium channel (Nav)-encoding genes are among early-onset epileptic encephalopathies (EOEE) targets, suggesting that other genes encoding Nav-binding proteins, such as fibroblast growth factor homologous factors (FHFs), may also play roles in these disorders.

Methods

To identify additional genes for EOEE, we performed whole-exome sequencing in a family quintet with 2 siblings with a lethal disease characterized by EOEE and cerebellar atrophy. The pathogenic nature and functional consequences of the identified sequence alteration were determined by electrophysiologic studies in vitro and in vivo.

Results

A de novo heterozygous missense mutation was identified in the FHF1 gene (FHF1AR114H, FHF1BR52H) in the 2 affected siblings. The mutant FHF1 pr

SUBMITTER: Siekierska A 

PROVIDER: S-EPMC4898311 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature