Clinical heterogeneity in familial epilepsy
Category: Current
Published Date
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The genetic basis of epilepsy is known to be highly complex. It displays genetic heterogeneity where different genes can cause the same epilepsy phenotype as well as clinical heterogeneity where the same gene can cause different epilepsy phenotypes. In the GABA receptor gene, two mutations have been found that result in a different phenotype, one mutation is seen in patients with childhood absence epilepsy (CAE) and febrile seizures, which are relatively mild forms of epilepsy, and in one family a mutation in the same gene results in severe myoclonic epilepsy of infancy (SMEI) which is an extremely severe condition with a poor prognosis. We are interested in the clinical heterogeneity of the GABA receptor gene and wish to understand how two different mutations in the same gene can cause two very different phenotypes. We have already made a mouse the mutation that gives rise to the less severe forms of epilepsy and we are now making a second mouse model with the GABA receptor mutation that gives rise to SMEI. Future work on these mice models will help us identify and understand the pathways leading to different types of epilepsy. Identification of the point of physiological divergence that results in these two conditions may yield important clues as to the fundamental mechanism of epileptogenesis in these different syndromes.
