title: Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures.
abstract: Epilepsies affect at least 2% of the population at some time in life, and many forms have genetic determinants. We have found a mutation in a gene encoding a GABA(A) receptor subunit in a large family with epilepsy. The two main phenotypes were childhood absence epilepsy (CAE) and febrile seizures (FS). There is a recognized genetic relationship between FS and CAE, yet the two syndromes have different ages of onset, and the physiology of absences and convulsions is distinct. This suggests the mutation has age-dependent effects on different neuronal networks that influence the expression of these clinically distinct, but genetically related, epilepsy phenotypes. We found that the mutation in GABRG2 (encoding the gamma2-subunit) abolished in vitro sensitivity to diazepam, raising the possibility that endozepines do in fact exist and have a physiological role in preventing seizures.
authors.affiliation: Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia, Australia. rwallace@wch.bionomics.com.au
authors.forename: R H
authors.initials: RH
authors.lastname: Wallace
authors.forename: C
authors.initials: C
authors.lastname: Marini
authors.forename: S
authors.initials: S
authors.lastname: Petrou
authors.forename: L A
authors.initials: LA
authors.lastname: Harkin
authors.forename: D N
authors.initials: DN
authors.lastname: Bowser
authors.forename: R G
authors.initials: RG
authors.lastname: Panchal
authors.forename: D A
authors.initials: DA
authors.lastname: Williams
authors.forename: G R
authors.initials: GR
authors.lastname: Sutherland
authors.forename: J C
authors.initials: JC
authors.lastname: Mulley
authors.forename: I E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: S F
authors.initials: SF
authors.lastname: Berkovic
mesh_terms: D017668:Age of Onset; D000927:Anticonvulsants / Q000494:pharmacology; D002648:Child; D020090:Chromosome Segregation; D003975:Diazepam / Q000494:pharmacology; D004594:Electrophysiology; D004832:Epilepsy, Absence / Q000235:genetics*; D005091:Exons; D005260:Female; D018757:GABA Modulators / Q000494:pharmacology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D021122:Protein Subunits; D011963:Receptors, GABA-A / Q000235:genetics*; D003294:Seizures, Febrile / Q000235:genetics*
chemical_list: D000927:Anticonvulsants; D018757:GABA Modulators; D021122:Protein Subunits; D011963:Receptors, GABA-A; D003975:Diazepam