Role of the phosphoinositide phosphatase FIG4 gene in familial epilepsy with polymicrogyria.

ABSTRACT:

Objective

The aim of this study was to identify the causal gene in a consanguineous Moroccan family with temporo-occipital polymicrogyria, psychiatric manifestations, and epilepsy, previously mapped to the 6q16-q22 region.

Methods

We used exome sequencing and analyzed candidate variants in the 6q16-q22 locus, as well as a rescue assay in Fig4-null mouse fibroblasts and immunohistochemistry of Fig4-null mouse brains.

Results

A homozygous missense mutation (p.Asp783Val) in the phosphoinositide phosphatase gene FIG4 was identified. Pathogenicity of the variant was supported by impaired rescue of the enlarged vacuoles in transfected fibroblasts from Fig4-deficient mice. Histologic examination of Fig4-null mouse brain revealed neurodevelopmental impairment in the hippocamp

SUBMITTER: Baulac S 

PROVIDER: S-EPMC3962989 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature