Referenced in: none

Automatically associated channels: Kir2.3

Title: Truncation of the GABA(A)-receptor gamma2 subunit in a family with generalized epilepsy with febrile seizures plus.

Authors: Louise A Harkin, David N Bowser, Leanne M Dibbens, Rita Singh, Fiona Phillips, Robyn H Wallace, Michaella C Richards, David A Williams, John C Mulley, Samuel F Berkovic, Ingrid E Scheffer, Steven Petrou

Journal, date & volume: Am. J. Hum. Genet., 2002 Feb , 70, 530-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11748509

Abstract
Recent findings from studies of two families have shown that mutations in the GABA(A)-receptor gamma2 subunit are associated with generalized epilepsies and febrile seizures. Here we describe a family that has generalized epilepsy with febrile seizures plus (GEFS(+)), including an individual with severe myoclonic epilepsy of infancy, in whom a third GABA(A)-receptor gamma2-subunit mutation was found. This mutation lies in the intracellular loop between the third and fourth transmembrane domains of the GABA(A)-receptor gamma2 subunit and introduces a premature stop codon at Q351 in the mature protein. GABA sensitivity in Xenopus laevis oocytes expressing the mutant gamma2(Q351X) subunit is completely abolished, and fluorescent-microscopy studies have shown that receptors containing GFP-labeled gamma2(Q351X) protein are retained in the lumen of the endoplasmic reticulum. This finding reinforces the involvement of GABA(A) receptors in epilepsy.