Epilepsies affect at least 2% of the population at some time in life, and m
any forms have genetic determinants(1,2). We have found a mutation in a gen
e encoding a GABA, receptor subunit in a large family with epilepsy. The tw
o main phenotypes were childhood absence epilepsy (CAE) and febrile seizure
s (FS), There is a recognized genetic: relationship between FS and CAE, yet
the two syndromes have different ages of onset, and the physiology of abse
nces and convulsions is distinct. This suggests the mutation has age-depend
ent effects on different neuronal networks that influence the expression of
these clinically distinct, but genetically related, epilepsy phenotypes. W
e 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.