Genes4Epilepsy: an epilepsy gene resource
- Author(s)
- Oliver, KL; Scheffer, IE; Bennett, MF; Grinton, BE; Bahlo, M; Berkovic, SF;
- Journal Title
- Epilepsia
- Publication Type
- epub ahead of print
- Abstract
- OBJECTIVE: "How many epilepsy genes are there?" is a frequently asked question. We sought to: 1) provide a curated list of genes that cause monogenic epilepsies, and 2) compare and contrast epilepsy gene panels from multiple sources. METHODS: We compared genes included on the epilepsy panels (as of 29-Jul-2022) of four clinical diagnostic providers: Invitae, GeneDx, Fulgent Genetics and Blueprint Genetics, and two research resources: PanelApp Australia and ClinGen. A master list of all unique genes was supplemented by additional genes identified via PubMed searches up until 15(th) Aug 2022 using search terms "genetics" AND/OR "epilepsy" AND/OR "seizures". Evidence supporting a monogenic role for all genes was manually reviewed; those with limited or disputed evidence were excluded. All genes were annotated according to inheritance pattern and broad epilepsy phenotype. RESULTS: Comparison of genes included on epilepsy clinical panels revealed high heterogeneity in both number of genes (range: 144-511) and content. Just 111 (15.5%) genes were included on all four clinical panels. Subsequent manual curation of all "epilepsy genes" identified >900 monogenic etiologies. Almost 90% of genes were associated with developmental and epileptic encephalopathies. By comparison only 5% of genes were associated with monogenic causes of "common epilepsies" (i.e. generalized and focal epilepsy syndromes). Autosomal recessive genes were most frequent (56% of genes); however, this varied according to the associated epilepsy phenotype(s). Genes associated with common epilepsy syndromes were more likely to be dominantly inherited and associated with multiple epilepsy types. SIGNIFICANCE: Our curated list of monogenic epilepsy genes is publicly available: github.com/bahlolab/genes4epilepsy, and will be regularly updated. This gene resource can be utilized to target genes beyond those included on clinical gene panels, for gene enrichment methods and candidate gene prioritization. We invite ongoing feedback and contributions from the scientific community via genes4-epilepsy@unimelb.edu.au.
- Publisher
- Wiley
- Keywords
- Monogenic disease; epilepsy panel; genetic architecture; pathogenic gene resource
- Research Division(s)
- Population Health And Immunity
- PubMed ID
- 36808730
- Publisher's Version
- https://doi.org/10.1111/epi.17547
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-03-08 03:16:03
Last Modified: 2023-03-08 04:02:34