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Clinical and Genetic Heterogeneity in Familial Temporal Lobe Epilepsy
Author(s) -
Santos N. F.,
Sousa S. C.,
Kobayashi E.,
Torres F. R.,
Sardinha J. A. F.,
Cendes F.,
LopesCendes I.
Publication year - 2002
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.43.s.5.23.x
Subject(s) - temporal lobe , penetrance , epilepsy , genotype , ictal , psychology , audiology , genetics , medicine , biology , phenotype , neuroscience , gene
Summary: Purpose: Familial forms of temporal lobe epilepsy have been described recently. A locus on ch 10q has been linked to partial epilepsy with auditory symptoms. We investigated the proportion of families segregating temporal lobe epilepsy (TLE) linked to ch 10q and sought to establish genotype–phenotype correlations. Methods: We studied 15 unrelated families segregating TLE. A total of 153 individuals, including 79 patients, were analyzed in this study. Family members were genotyped for four polymorphic dinucleotide repeat markers: D10S185, D10S574, D10S577, and D10S192, which flank the 15‐cM candidate interval on ch 10q. Two‐point lod scores were calculated for each family separately. Results: Fourteen of our families had ictal semiology of mesial temporal onset of seizures and magnetic resonance imaging (MRI) abnormalities in the mesial structures; only one family, with seven affected individuals, reported auditory symptoms and had normal MRIs. Pedigree analysis showed an autosomal dominant transmission with 0.75 penetrance. Only two families had informative lod scores. A large family, with 22 affected individuals segregating mesial TLE, had negative lod scores for all four markers genotyped. The lod scores were significantly negative (less than –2.00) up to 0.05 for D10S185, 0.10 for D10S574, 0.25 for D10S577, and 0.15 for D10S192. The single family with auditory symptoms had positive lod scores for all markers genotyped, with a Z max of 1.52 at 0.0 for D10S574. Conclusions: We identified two different clinical groups of families segregating TLE. Most families identified in this study had mesial TLE. Only one single family segregating lateral TLE was found. We significantly excluded linkage between familial mesial TLE and the locus on ch 10q. In addition, we showed evidence for linkage between one family with lateral TLE and markers on ch 10q. This is strong evidence for clinical and genetic heterogeneity among familial forms of TLE.