Mapping of genes predisposing to idiopathic generalized epilepsy.
Idiopathic generalized epilepsy (IGE) is characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Twin and family studies suggest that genetic factors play a key part in IGE. A multilocus model appears to best fit the observed inheritance patterns. Mapping of IGE-related genes has been previously attempted using parametric methods, with conflicting results. In particular, recent evidence argues both for and against a chromosome 6p locus (EJM1) for juvenile myoclonic epilepsy, a subtype of IGE. We have approached the problem of mapping IGE loci using non-parametric methods, which have recently been successful for other complex diseases. No evidence for linkage to chromosome 6p was obtained. However, we obtained evidence for involvement of a locus at chromosome 8q24, close to the marker D8S256. The same 8q24 region was previously implicated in families with benign neonatal familial convulsions (BNFC), a generalized epilepsy syndrome that is inherited as a simple dominant mendelian trait. There is an apparent conserved syntenic group of genes in human 8q24 and a region of mouse chromosome 15, which harbors the stargazer (stg) locus. Homozygous mutant mice at the stg locus show a form of generalized epilepsy that resembles human absence epilepsy. Our findings may have implications for a locus on 8q24 predisposing to IGE.
Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
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Zara
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Bianchi
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Avanzini
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Di Donato
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Castellotti
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Patel
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Pandolfo
D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004198:Disease Susceptibility; D004829:Epilepsy, Generalized / Q000235:genetics*; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D010375:Pedigree