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Caractérisation de variants génétiques de vulnérabilité à l'épilepsie chez des familles Algériennes

Abstract : A genetic component to epilepsy has been recognized since Antiquity and is well established through twin and familial aggregation studies, which provide convincing evidence for the heritability of epilepsy. Despite major advances in genetic studies, genetic epilepsies have not yet revealed all their secrets. This prospective study aimed to identify genetic variants of epilepsy, to document the genotype/phenotype correlations and inheritance patterns in multigenerational Algerian families. Genetic analyzes included exome sequencing, CGH-array and Southern blotting. We studied a family with a pair of monozygotic twins affected by temporal lobe epilepsy. Exome sequencing revealed that both twins carried a novel de novo mutation (p.A39E) in the GAL gene encoding the galanin neuropeptide. This latter was found to act as a potent anticonvulsant and regulates epileptic seizures in animal models. However, until now its role in human epilepsy was not established. Functional analysis showed evidence that the mutant protein disrupts galanin signalling, and strongly supports GAL as the causal gene for the TLE in this family. We described a family with two siblings affected by temporal lobe epilepsy and psychiatric comorbidities. Exome sequencing identified a single nucleotide polymorphism in the RELN gene (rs55689103) whose mutations have been associated with epilepsy and schizophrenia. We identified two families with progressive myoclonus epilepsy type 1. Genetic studies by Southern blotting showed an expansion of dodecamer CCCCGCCCCGCG in EPM1 gene. In addition, two other families were analysed by CGH-array, but no pathogenic CNV was identified. The study of other multigenerational families would identify new genetic variants of epilepsy.
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https://tel.archives-ouvertes.fr/tel-01672987
Contributor : Amina Chentouf <>
Submitted on : Thursday, December 28, 2017 - 7:48:48 AM
Last modification on : Monday, October 19, 2020 - 11:07:17 AM

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  • HAL Id : tel-01672987, version 1

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Amina Chentouf. Caractérisation de variants génétiques de vulnérabilité à l'épilepsie chez des familles Algériennes. Génétique humaine. Faculté de Médecine d'Oran, Université Oran 1, 2016. Français. ⟨tel-01672987⟩

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