Genetic factors play a major role in the aetiology of idiopathic generalise
d epilepsies (IGEs). The present genome scan was designed to identify susce
ptibility loci that predispose to a spectrum of common IGE syndromes. Our c
ollaborative study included 130 IGE-multiplex families ascertained through
a proband with either an idiopathic absence epilepsy or juvenile myoclonic
epilepsy, and one or more siblings affected by an IGE trait, In total, 413
microsatellite polymorphisms were genotyped in 617 family members. Non-para
metric multipoint linkage analysis, using the GeneHunter program, provided
significant evidence for a novel IGE susceptibility locus on chromosome 3q2
6 (Z(NPL) = 4.19 at D3S3725; P = 0.000017) and suggestive evidence for two
IGE loci on chromosome 14q23 (Z(NPL) = 3.28 at D14S63; P = 0.000566), and c
hromosome 2q36 (Z(NPL) = 2.98 at D2S1371; P = 0.000535). The present linkag
e findings provide suggestive evidence that at least three genetic factors
confer susceptibility to generalised seizures in a broad spectrum of IGE sy
ndromes. The chromosomal segments identified harbour several genes involved
in the regulation of neuronal ion influx which are plausible candidates fo
r mutation screening.