Sanjay M Sisodiya1, Heather C Mefford. 1. The Epilepsy Society, Chalfont St Peter, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. sisodiya@ion.ucl.ac.uk
Abstract
PURPOSE OF REVIEW: We review key findings over the past year in the genetics of the common epilepsies and consider their impact on the field. RECENT FINDINGS: There have been important discoveries across two major aspects of genetics of the common epilepsies. Firstly, the first genome-wide association study in epilepsy has been published, for the focal epilepsies. With reasonable power to detect even modest effect sizes, the absence of genome-wide significant association demands refinement of further single-nucleotide polymorphism (SNP)-based genome-wide approaches, with a focus on more homogeneous phenotypes. Secondly, several putatively causal variants of a different type, copy number variants (CNVs), have been discovered. Several recurrent epilepsy-associated CNVs have been identified, including microdeletions at 15q13.3 and 16p13.11. CNVs constitute the commonest known genetic cause of the epilepsies. How CNVs cause disease, and why the same CNV can cause different diseases is unexplained. Nevertheless, CNVs will accelerate discovery of 'epilepsy genes', focussing attention on specific genomic regions. With the published genome-wide SNP study, CNVs are redirecting research efforts to a search for rare variants underlying common epilepsies. CNVs have also highlighted the challenges ahead in genotype-phenotype correlation. SUMMARY: Major discoveries are reshaping the genetics of the common epilepsies and prefiguring whole exome/whole genome resequencing efforts.
PURPOSE OF REVIEW: We review key findings over the past year in the genetics of the common epilepsies and consider their impact on the field. RECENT FINDINGS: There have been important discoveries across two major aspects of genetics of the common epilepsies. Firstly, the first genome-wide association study in epilepsy has been published, for the focal epilepsies. With reasonable power to detect even modest effect sizes, the absence of genome-wide significant association demands refinement of further single-nucleotide polymorphism (SNP)-based genome-wide approaches, with a focus on more homogeneous phenotypes. Secondly, several putatively causal variants of a different type, copy number variants (CNVs), have been discovered. Several recurrent epilepsy-associated CNVs have been identified, including microdeletions at 15q13.3 and 16p13.11. CNVs constitute the commonest known genetic cause of the epilepsies. How CNVs cause disease, and why the same CNV can cause different diseases is unexplained. Nevertheless, CNVs will accelerate discovery of 'epilepsy genes', focussing attention on specific genomic regions. With the published genome-wide SNP study, CNVs are redirecting research efforts to a search for rare variants underlying common epilepsies. CNVs have also highlighted the challenges ahead in genotype-phenotype correlation. SUMMARY: Major discoveries are reshaping the genetics of the common epilepsies and prefiguring whole exome/whole genome resequencing efforts.
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