title: Molecular biology of epilepsy genes.
abstract: Multifactorial inheritance is the most important model accounting for the genetic behavior of the common epilepsies. Important to this model is the concept that many cumulative or synergistic risk genes ultimately lead to a threshold effect. Sophisticated molecular testing indicates that the common epilepsies are very polygenic without evidence of any single gene having even a mild-to-modest risk effect. However, enrichment of copy number variants in cohorts of individuals with epilepsy indicates that certain structural changes in the genome can confer significant risk for epilepsy. The mechanisms whereby copy number variants confer this effect are not yet known. The study of epilepsy due to single gene defects however has helped clarify certain seizure mechanisms. For example, discoveries using animal models of SCN1A or ARX mutations implicate a predominant role for interneurons due to disturbed GABAergic function. It is hoped that future genetic and neurobiological studies will provide better insight into how multiple genes contribute to the common epilepsies.
authors.affiliation: Raymond C. Philips Unit, Division of Genetics and Metabolism, Department of Pediatrics, University of Florida, Gainesville, FL 32605, USA. willicx@peds.ufl.edu
authors.forename: Charles A
authors.initials: CA
authors.lastname: Williams
authors.forename: Agatino
authors.initials: A
authors.lastname: Battaglia
mesh_terms: D004827:Epilepsy / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008967:Molecular Biology; D020412:Multifactorial Inheritance / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: C469264:ARX protein, human; D018398:Homeodomain Proteins; D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human; D014157:Transcription Factors