Role of the Phosphoinositide Phosphatase FIG4 Gene in Familial Epilepsy with Polymicrogyria

Overview

Journal Neurology

Specialty Neurology

Date 2014 Mar 7

PMID 24598713

Citations 39

Authors

Stephanie Baulac

Guy M Lenk

Beatrice Dufresnois

Bouchra Ouled Amar Bencheikh

Philippe Couarch

Julie Renard

Peter A Larson

Cole J Ferguson

Eric Noe

Karine Poirier

Christine Hubans

Stephanie Ferreira

Renzo Guerrini

Reda Ouazzani

Khalid Hamid El Hachimi

Miriam H Meisler

Eric Leguern

Affiliations

Soon will be listed here.

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 hippocampus, cortex, and cerebellum as well as impaired cerebellar gyration/foliation reminiscent of human cortical malformations.

Conclusions: This study extends the spectrum of phenotypes associated with FIG4 mutations to include cortical malformation associated with seizures and psychiatric manifestations, in addition to the previously described Charcot-Marie-Tooth disease type 4J and Yunis-Varón syndrome.

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