Molecular pathology of genetic epilepsies associated with GABAA receptor subunit mutations.
Mutations in ligand-gated ion channel genes associated with idiopathic generalized epilepsies have been reported in excitatory acetylcholine receptor alpha4 and beta2 subunit genes linked to autosomal dominant nocturnal frontal lobe epilepsy and in inhibitory GABA(A) receptor alpha1, beta3, gamma2, and delta subunit genes associated with childhood absence epilepsy, juvenile myoclonic epilepsy, pure febrile seizures, generalized epilepsy with febrile seizures plus, and generalized epilepsy with tonic-clonic seizures. Recent studies suggest that these mutations alter receptor function or biogenesis, including impaired receptor subunit messenger RNA stability, receptor subunit protein folding and stability, receptor assembly, and receptor trafficking.
Macdonald
Robert L
RL
Departments of Neurology, Vanderbilt University, Nashville, Tennessee, USA. Robert.Macdonald@vanderbilt.edu
Kang
Jing-Qiong
JQ