title: Epilepsy genes and the genetics of epilepsy syndromes: the promise of new therapies based on genetic knowledge.
abstract: Treatment strategies based on the molecular biology of the epilepsies may soon become a reality. Critical steps in this process are identifying molecular genetic defects in specific epilepsies, understanding of the neurobiologic consequences of those defects, and developing methods to correct the molecular defects or their downstream consequences. Identification of molecular defects is easier in single-gene epilepsies than in those with complex inheritance, although the latter are more common. A number of epilepsies have been mapped and, in two cases, specific genes have been identified. Unverricht-Lundborg disease is caused by defects in the cystatin B gene, with absence of the gene product. Autosomal dominant nocturnal frontal lobe epilepsy in some families is caused by mutations in the alpha4-subunit of the nicotinic acetylcholine receptor gene. In vitro studies suggest that the mutations lead to impaired function of the acetylcholine receptor, raising the possibility of cholinergic therapy for this condition. Advances in the molecular biology of the epilepsies are likely to change our understanding radically and to allow opportunities to develop innovative new treatments for epilepsy.
authors.affiliation: Department of Medicine (Neurology), University of Melbourne, Austin and Repatriation Medical Centre, Victoria, Australia.
authors.forename: S F
authors.initials: SF
authors.lastname: Berkovic
mesh_terms: D000818:Animals; D055313:Cystatin B; D015891:Cystatins / Q000235:genetics / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004831:Epilepsies, Myoclonic / Q000235:genetics / Q000378:metabolism; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D017034:Epilepsy, Frontal Lobe / Q000235:genetics / Q000378:metabolism; D005190:Family; D015870:Gene Expression; D005799:Genes, Dominant / Q000235:genetics; D008040:Genetic Linkage; D015316:Genetic Therapy; D005838:Genotype; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008967:Molecular Biology; D009154:Mutation; D010641:Phenotype; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism; D013577:Syndrome
chemical_list: C524994:CSTB protein, human; C524992:Cstb protein, mouse; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D011950:Receptors, Cholinergic; D055313:Cystatin B