Abstract
Epilepsies 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 γ2-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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Acknowledgements
We thank B. Cromer for discussions and the family for participation. Supported by the National Health & Medical Research Council, Australian Research Council, Women's & Children's Hospital Foundation, National Heart Foundation, Bionomics Limited and a University of Melbourne Scholarship (to C.M.).
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Wallace, R., Marini, C., Petrou, S. et al. Mutant GABAA receptor γ2-subunit in childhood absence epilepsy and febrile seizures. Nat Genet 28, 49–52 (2001). https://doi.org/10.1038/ng0501-49
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DOI: https://doi.org/10.1038/ng0501-49
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