Abstracts

The association between temporal lobe epilepsy and mesial temporal sclerosis (MTS) has been well established; as well as the use of hippocampal atrophy (HA) on magnetic resonance imaging (MRI) as an [italic]in vivo[/italic] surrogate marker of MTS. One of the risk factors associated to MTS is childhood prolonged febrile seizures. We have described a type of mesial temporal lobe epilepsy with evident familial recurrence associate with HA but low frequency of febrile seizures. Previous pedigree and complex segregation analyses provided evidence for the presence of a major gene predisposing to HA in familial mesial temporal lobe epilepsy (FMTLE). The objective of this study was to identify the region harboring the main gene associated with HA in FMTLE by a genome-wide linkage study., Genome-wide scan was performed using a total of 332 microsatellite markers at [sim]12cM intervals. An additional 14 markers were genotyped in the candidate region. Two-point and multipoint LOD scores were calculated with the LINKAGE computer package. We assumed an autosomal dominant inheritance with incomplete penetrance., We identified linkage to chromosome 18p11.3-11.2, with a maximum LOD score of 3.60 at [theta]= 0.0 for the D18S976 marker in a single family (F-10) with 11 affected individuals with HA. Multipoint and haplotype analyses localized the locus within a 6 cM interval flanked by markers D18S976 and D18S452. No other significantly positive LOD score was detected for this family in the entire genome., This is the first conclusive evidence that HA may be caused by genetic factors, which can have major implications in the study of the pathophysiological mechanisms underlying MTS and its relationship with temporal lobe epilepsy., (Supported by FAPESP.)