Genes and molecular mechanisms involved in the epileptogenesis of idiopathic absence epilepsies.
Idiopathic absence epilepsies (IAE), that have high prevalence particularly among children and adolescents, are complex disorders mainly caused by genetic factors. Childhood absence epilepsy and juvenile absence epilepsy are among the most common subtypes of IAEs. While the role of ion channels has been the primary focus of epilepsy research, the analysis of mutation and association in both patients with absence epilepsies and animal models revealed the involvement of GABA receptors and calcium channels, but also of novel non-ion channel proteins in inducing spike wave discharges (SWD). Functional studies on a mutated variant of these proteins also support their role in the epileptogenesis of absence seizures. Studies in animal models point to both the thalamus and cortex as the origin of SWDs: the abnormalities in the components of these circuits leading to seizure activity. This review examines the current research on mutations and susceptibility alleles determined in the genes that code for the subunits of GABA receptors (GABRG2, GABRA1, GABRB3, GABRA5, GABA(B1) and GABA(B2)), calcium channels (CACNA1A, CACNA1G, CACNA1H, CACNA1I, CACNAB4, CACNAG2 and CACNG3), and novel non-ion channel proteins, taking into account the results of functional studies on these variants.
Department of Molecular Biology and Genetics, T.C. Istanbul Arel University, Tepekent-Buyukcekmece, Istanbul, Turkey. ozlemyalcin@arel.edu.tr
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D000293:Adolescent; D000483:Alleles; D000818:Animals; D015220:Calcium Channels / Q000235:genetics* / Q000502:physiology; D002648:Child; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D018079:Receptors, GABA / Q000235:genetics* / Q000378:metabolism; D012640:Seizures / Q000209:etiology / Q000235:genetics; D013788:Thalamus / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000235:genetics
D015220:Calcium Channels; D007473:Ion Channels; D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid