A structural look at GABAA receptor mutations linked to epilepsy syndromes

Understanding the genetic variation in GABA(A) receptor subunit genes (GABRs), GABRA1-6, GABRB1-3, GABRG1-3 and GABRD, in individuals affected by epilepsy may improve the diagnosis and treatment of epilepsy syndromes through identification of disease-associated variants. However, the lack of functional analysis and validation of many novel and previously reported familial and de novo mutations have made it challenging to address meaningful gene associations with epilepsy syndromes. GABA(A) receptors belong to the Cys-loop receptor family. Even though GABA(A) receptor mutant residues are widespread among different GABRs, their frequent occurrence in important structural domains that share common functional features suggests associations between structure and function.