Abstracts

RATIONALE: Susceptibility genes in idiopathic generalized epilepsy (IGE) may be shared betweeen subtypes and/or be subtype specific. We are performing association studies of common IGE's, focusing initially on shared susceptibility genes. As numbers increase we will look for subtype specific association. METHODS: Using cheek swabs or blood, so far we collected DNA from more than a) 200 unselected IGE probands with generalised spike wave on EEG and a compatible clinical presentation b) matched controls c) available parents. The clinical database includes seizure-types and age of onset, history of febrile convulsions, seizure patterns and trigger factors, EEG findings, imaging data, response to treatment, and family history. Where the phenotype is typical, the epilepsy syndrome is classified by IGE subtype as per the ILAE classification. Genetic association studies are performed using biallelic or microsatellite markers in candidate genes. RESULTS: Positive associations presented so far using the unselected IGE sample include a) two markers in CACNA1A, the ?1A calcium channel subunit gene; exon 8 (p=0.0005), which is confirmed by within family analysis, and intron 7 (p=0.032), and b) a positive association with two markers, D15S1360 and D15S1031, at 15q13-q14 (which includes the ?7-nicotinic acetyl choline receptor subunit gene), although within family studies in one marker suggest a possible population artifact. Negative associations to date include the ?4-nicotinic acetyl choline receptor subunit and metabotropic glutamate receptor subunits 7 and 8. CONCLUSIONS: The clinical data and correlation with the above positive genotype results will be presented. Ref: Chioza BA et al Neurology 54 April 2000 (Suppl 3) p A355 Goodwin HJ et al. Neurology 54 April 2000 (Suppl 3) p A356 Supported by the Epilepsy Research Foundation, Fund for Epilepsy and King's College Joint Research Fund