MAPPING OF GENES PREDISPOSING TO IDIOPATHIC GENERALIZED EPILEPSY

Idiopathic generalized epilepsy (IGE) is characterized by recurring ge neralized seizures in the absence of detectable brain lesions and/or m etabolic abnormalities, Twin and family studies suggest that genetic f actors play a key part in IGE. A multilocus model appears to best fit the observed inheritance patterns, Mapping of ICE-related genes has be en previously attempted using parametric methods, with conflicting res ults, In particular, recent evidence argues both for and against a chr omosome 6p locus (EJM1) for juvenile myoclonic epilepsy, a subtype of IGE, We have approached the problem of mapping IGE loci using non-para metric methods, which have recently been successful for other complex diseases, No evidence for linkage to chromosome 6p was obtained, Howev er, we obtained evidence for involvement of a locus at chromosome 8q24 , close to the marker D8S256, The same 8q24 region was previously impl icated 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 gene s 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, O ur findings may have implications for a locus on 8q24 predisposing to IGE.