Identification of epilepsy genes in human and mouse

The development of molecular markers and genomic resources has facilitated the isolation of genes responsible for rare monogenic epilepsies in human and mouse. Many of the identified genes encode ion channels or other components of neuronal signaling. The electrophysiological properties of mutant al...

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Bibliographic Details
Published in:Annual review of genetics 2001-01, Vol.35 (1), p.567-588
Main Authors: Meisler, M H, Kearney, J, Ottman, R, Escayg, A
Format: Article
Language:English
Subjects:
Analysis
Animals
Disease Models, Animal
Epilepsy
Epilepsy - genetics
Genes
Genetic aspects
Genetic Linkage
Genetic research
Genetics
Heterogeneity
Humans
Ion channels
Mice
Mice, Mutant Strains
Mutation
Mutation (Biology)
NAV1.1 Voltage-Gated Sodium Channel
Nerve Tissue Proteins - chemistry
Nerve Tissue Proteins - genetics
Phenotype
Potassium Channels - genetics
Receptors, Cholinergic - genetics
Receptors, Nicotinic - genetics
Rodents
Sodium channels
Sodium Channels - chemistry
Sodium Channels - genetics
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Summary:The development of molecular markers and genomic resources has facilitated the isolation of genes responsible for rare monogenic epilepsies in human and mouse. Many of the identified genes encode ion channels or other components of neuronal signaling. The electrophysiological properties of mutant alleles indicate that neuronal hyperexcitability is one cellular mechanism underlying seizures. Genetic heterogeneity and allelic variability are hallmarks of human epilepsy. For example, mutations in three different sodium channel genes can produce the same syndrome, GEFS+, while individuals with the same allele can experience different types of seizures. Haploinsufficiency for the sodium channel SCN1A has been demonstrated by the severe infantile epilepsy and cognitive deficits in heterozygotes for de novo null mutations. Large-scale patient screening is in progress to determine whether less severe alleles of the genes responsible for monogenic epilepsy may contribute to the common types of epilepsy in the human population. The development of pharmaceuticals directed towards specific epilepsy genotypes can be anticipated, and the introduction of patient mutations into the mouse genome will provide models for testing these targeted therapies.
ISSN:0066-4197
1545-2948
DOI:10.1146/annurev.genet.35.102401.091142