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Objectives: Mutations in the EFHC1 gene have been reported in six juvenile myoclonic epilepsy (JME) families from Mexico and Belize. In this study, we screened 27 unrelated JME Italian families for mutations in the EFHC1 gene., Materials and Methods: Twenty-seven families (86 affected individuals, 52 women) with at least two affected members with JME were selected. DNA was isolated from peripheral blood lymphocytes by standard methods and each exon of the EFHC1 gene was amplified and sequenced using intronic primers., Results: Two heterozygous mutations were identified in three unrelated families. One (R353 W) was a novel missense mutation, while the F229 L mutation was previously described (say which on of the two occurred in two families). Both mutations cosegregated with the disease. In a fourth family, the variant 545G-->A (resulting in the amino acid substitution R182 H) cosegregated with JME., Conclusions: The results of our study extend the distribution of EFHC1 mutations to the white population and confirm the high level of genetic heterogeneity associated with JME.

Purpose: To clarify the possible role of other factors including the ApoE epsilon4 allele for memory decline in temporal lobe epilepsy (TLE)., Methods: We conducted a neuropsychological and molecular study in 138 consecutive patients (78 female patients; mean age, 50.2 years, SD +/- 17.9; range, 14 to 87 years) with mild nonlesional TLE, who rarely or never had seizures at long-term follow-up. The mean age at seizure onset was 33.0 years (SD, +/-21.7), and the mean duration of epilepsy was 17.1 years (SD, +/-15.7)., Results: Thirty-four (25%) of 138 patients had test scores indicating verbal learning deficit (VLD). The presence of an ApoE epsilon4 allele was associated with an increased risk of VLD (OR, 4.18; 95% CI, 1.66-10.55). The effect of the ApoE genotype was independent of both the age at epilepsy onset and disease duration as well as of a low educational level, which were separately associated with VLD (p values = 0.045, 0.001, and 0.001, respectively). A significant linear trend (p = 0.005) was seen in the relation between disease duration and cognitive impairment, with the highest risk being in patients with an epilepsy duration > or =25.5 years (OR, 7.06; 95% CI, 1.67-29.85), especially if they carried the epsilon4 allele (OR, 32.29; 95% CI, 5.23-195.72)., Conclusions: These results provide evidence for an alteration in cognitive performance as a function of the presence of the ApoE epsilon4 allele and point to the critical role of disease duration itself for cognitive impairment in TLE.

Background: Dysfunction of gamma-aminobutyric acid (GABA) (B) receptors has been implicated in the pathogenesis of temporal lobe epilepsy (TLE)., Objective: To evaluate the genetic contribution of cloned human GABA(B) receptors to TLE., Methods: The authors genotyped 141 patients (78 women and 63 men; mean age = 49.1 +/- 18.0 years) with nonlesional TLE and 372 age- and sex-matched normal individuals for the known polymorphism G1465A in the human GABA(B) receptor 1 [GABA(B[1])] gene., Results: There was a highly significant overrepresentation of the G1465A heterozygote in patients with TLE compared with controls. The A/G genotype was found in 17% of the 141 patients with TLE and in only 0.5% of the 372 controls (p < 0.0001). The authors also found that patients carrying the A allele had a significantly higher risk (p = 0.003, OR = 6.47, 95% CI = 2.02 to 20.76) of developing drug-resistant TLE. Furthermore, the age at onset of seizures tended to be lower in patients with A/G genotype, but the difference was not significant., Conclusions: The results of this study indicate that the GABA(B[1]) polymorphism (G1465A) confers a highly increased susceptibility to TLE. Moreover, it seems to influence the severity of this common epileptic disorder.

Purpose: To evaluate whether the inheritance of the apolipoprotein E (ApoE) epsilon4 allele is a risk factor for nonlesional temporal lobe epilepsy (TLE), and to determine whether the newly described -491 A/T ApoE polymorphism may independently affect the risk of nonlesional TLE., Methods: The study group consisted of 63 patients (35 women and 28 men; age at onset of epilepsy, 30.6 +/- 19.6 years; mean (+/-SD). All of them had received a diagnosis of nonlesional TLE after a detailed clinical, electroencephalographic, and brain magnetic resonance investigation. The ApoE polymorphisms were determined from blood samples by standard methods. The molecular study also was performed in 220 age- and sex-matched normal individuals., Results: There were no differences between TLE patients and controls in either allelic or genotypic frequencies of the ApoE and -491A/T polymorphisms. Moreover, no effect of ApoE or -491A/T polymorphisms was found on the age at onset and severity of epilepsy., Conclusions: The allelic and genotypic frequencies of ApoE polymorphisms in Italian patients with nonlesional TLE are comparable to control values, indicating that ApoE polymorphisms are not a significant genetic risk factor for the occurrence of nonlesional TLE.