Role of the phosphoinositide phosphatase FIG4 gene in familial epilepsy with polymicrogyria.
Neurology
; 82(12): 1068-75, 2014 Mar 25.
Article
en En
| MEDLINE
| ID: mdl-24598713
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Cromosomas Humanos Par 6
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Epilepsia
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Malformaciones del Desarrollo Cortical
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Flavoproteínas
Límite:
Adult
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Animals
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Female
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Humans
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Male
País/Región como asunto:
Africa
Idioma:
En
Revista:
Neurology
Año:
2014
Tipo del documento:
Article