title: Truncation of the GABA(A)-receptor gamma2 subunit in a family with generalized epilepsy with febrile seizures plus.
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.
authors.affiliation: Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, Adelaide, South Australia, Australia. lharkin@wch.bionomics.com.au
authors.forename: Louise A
authors.initials: LA
authors.lastname: Harkin
authors.forename: David N
authors.initials: DN
authors.lastname: Bowser
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Dibbens
authors.forename: Rita
authors.initials: R
authors.lastname: Singh
authors.forename: Fiona
authors.initials: F
authors.lastname: Phillips
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Wallace
authors.forename: Michaella C
authors.initials: MC
authors.lastname: Richards
authors.forename: David A
authors.initials: DA
authors.lastname: Williams
authors.forename: John C
authors.initials: JC
authors.lastname: Mulley
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: Steven
authors.initials: S
authors.lastname: Petrou
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018388:Codon, Terminator / Q000235:genetics; D004594:Electrophysiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004831:Epilepsies, Myoclonic / Q000150:complications / Q000235:genetics; D004829:Epilepsy, Generalized / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010375:Pedigree; D011487:Protein Conformation; D021122:Protein Subunits; D011963:Receptors, GABA-A / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D003294:Seizures, Febrile / Q000150:complications / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D018388:Codon, Terminator; D021122:Protein Subunits; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid