Nature Genetics
28, 49 - 52 (2001)
doi:10.1038/ng0501-49
Mutant GABAA receptor  2-subunit in childhood absence epilepsy and febrile seizuresRobyn H. Wallace1, 2, Carla Marini4, Steven Petrou5, Louise A. Harkin1, 2, David N. Bowser5, Rekha G. Panchal5, David A. Williams5, Grant R. Sutherland1, 2, 3, John C. Mulley1, 3, Ingrid E. Scheffer4, 6
& Samuel F. Berkovic4, 61
Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia, Australia. 2
Department of Paediatrics, University of Adelaide, Adelaide, South Australia, Australia. 3
Department of Genetics, University of Adelaide, Adelaide, South Australia, Australia. 4
Epilepsy Research Institute and Department of Medicine (Neurology), University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg, Victoria, Australia. 5
Department of Physiology, University of Melbourne, Parkville, Victoria, Australia. 6
Department of Neurology, Royal Children's Hospital, Victoria, Australia.
Correspondence should be addressed to Robyn H. Wallace rwallace@wch.bionomics.com.auEpilepsies affect at least 2% of the population at some time in life, and many forms have genetic determinants1,
2. We have found a mutation in a gene encoding a GABAA 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  2-subunit) abolished in vitro sensitivity to diazepam, raising the possibility that endozepines do in fact exist and have a physiological role in preventing seizures.
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