Genes4Epilepsy: An epilepsy gene resource

Area of Science:

• Genetics
• Neurology
• Medical Research

Background:

• Epilepsy is a neurological disorder with numerous genetic causes.
• Identifying all genes responsible for monogenic epilepsies is crucial for diagnosis and research.
• Current clinical gene panels for epilepsy show considerable heterogeneity.

Purpose of the Study:

• To create a comprehensive, curated list of genes associated with monogenic epilepsies.
• To compare and contrast the content of epilepsy gene panels from various clinical diagnostic providers and research resources.
• To establish a publicly available resource for epilepsy gene research.

Main Methods:

• Compared genes on epilepsy panels from four clinical providers and two research resources.
• Compiled a master list of unique genes, supplemented by PubMed searches.
• Manually reviewed evidence for monogenic epilepsy causation, excluding disputed genes.
• Annotated genes by inheritance pattern and epilepsy phenotype.

Main Results:

• High heterogeneity observed in the number and content of clinical epilepsy gene panels (144-511 genes).
• Only 111 genes (15.5%) were common across all four clinical panels.
• Curated list identified over 900 monogenic epilepsy etiologies.
• Approximately 90% of identified genes are linked to developmental and epileptic encephalopathies, while only 5% relate to common epilepsy syndromes.
• Autosomal recessive inheritance was most frequent (56%), particularly for certain phenotypes.

Conclusions:

• A comprehensive list of monogenic epilepsy genes has been established and is publicly available.
• The curated list surpasses the scope of current clinical gene panels, offering broader research utility.
• This resource supports gene enrichment, candidate gene prioritization, and future research into epilepsy genetics.
• Ongoing community contributions are invited to maintain and expand the gene resource.