title: Childhood absence epilepsy and febrile seizures: a family with a GABA(A) receptor mutation.
abstract: Although several genes for idiopathic epilepsies from families with simple Mendelian inheritance have been found, genes for the common idiopathic generalized epilepsies, where inheritance is complex, presently are elusive. We studied a large family with epilepsy where the two main phenotypes were childhood absence epilepsy (CAE) and febrile seizures (FS), which offered a special opportunity to identify epilepsy genes. A total of 35 family members had seizures over four generations. The phenotypes comprised typical CAE (eight individuals); FS alone (15), febrile seizures plus (FS(+)) (three); myoclonic astatic epilepsy (two); generalized epilepsy with tonic-clonic seizures alone (one); partial epilepsy (one); and unclassified epilepsy despite evaluation (two). In three remaining individuals, no information was available. FS were inherited in an autosomal dominant fashion with 75% penetrance. The inheritance of CAE in this family was not simple Mendelian, but suggestive of complex inheritance with the involvement of at least two genes. A GABA(A) receptor gamma2 subunit gene mutation on chromosome 5 segregated with FS, FS(+) and CAE, and also occurred in individuals with the other phenotypes. The clinical and molecular data suggest that the GABA(A) receptor subunit mutation alone can account for the FS phenotype. An interaction of this gene with another gene or genes is required for the CAE phenotype in this family. Linkage analysis for a putative second gene contributing to the CAE phenotype suggested possible loci on chromosomes 10, 13, 14 and 15. Examination of these loci in other absence pedigrees is warranted.
authors.affiliation: Epilepsy Research Institute, The University of Melbourne, Austin and Repatriation Medical Centre, West Heidelberg, Victoria, Australia.
authors.forename: Carla
authors.initials: C
authors.lastname: Marini
authors.forename: Louise A
authors.initials: LA
authors.lastname: Harkin
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Wallace
authors.forename: John C
authors.initials: JC
authors.lastname: Mulley
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
mesh_terms: D000328:Adult; D002675:Child, Preschool; D002882:Chromosomes, Human, Pair 13; D002883:Chromosomes, Human, Pair 14; D002884:Chromosomes, Human, Pair 15; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D011963:Receptors, GABA-A / Q000235:genetics*; D003294:Seizures, Febrile / Q000150:complications* / Q000235:genetics / Q000503:physiopathology
chemical_list: D011963:Receptors, GABA-A