title: Making sense of nonsense GABA(A) receptor mutations associated with genetic epilepsies.
abstract: Nonsense mutations that generate premature translation-termination codons (PTCs) are responsible for approximately one- third of human genetic diseases. PTCs in both voltage- and ligand-gated ion channel genes, including those for sodium, potassium, nicotinic cholinergic receptor and GABA(A) receptor channels, have been associated with genetic epilepsies but the epilepsy syndromes they cause are variable. It was recently proposed that two well-established molecular pathways, nonsense-mediated decay (NMD) and endoplasmic reticulum-associated degradation (ERAD), determine the effects of PTCs in GABA(A) receptor subunit genes associated with genetic epilepsies on the cellular fates of mutant subunit mRNAs and proteins. Activation of these different molecular mechanisms might contribute in part to different clinical phenotypes in patients with GABA(A) receptor subunit gene PTCs and thus different approaches for treatment of their genetic epilepsies might be required.
authors.affiliation: Department of Neurology, Vanderbilt University, Nashville, TN 37232-8552, USA. jingqiong.kang@vanderbilt.edu
authors.forename: Jing-Qiong
authors.initials: JQ
authors.lastname: Kang
authors.forename: Robert L
authors.initials: RL
authors.lastname: Macdonald
mesh_terms: D000818:Animals; D018389:Codon, Nonsense; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D006801:Humans; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism
chemical_list: D018389:Codon, Nonsense; D011963:Receptors, GABA-A