Abstracts

The purpose of our study was to determine if mutations in the Leucine Rich Glioma Inactivated 1 gene (LGI1) contribute to the development of both lateral(LTLE) and mesial temporal lobe epilepsy(MTLE). Our hypothesis was driven by the 1) occasional reports of auditory symptoms in familial MTLE patients and 2) the presence of mesial symptoms such as deja vu and epigastric aura in familial LTLE patients with mutations in the LGI1 gene. Genomic DNA was extracted from 34 temporal lobe epilepsy(TLE) patients. A preliminary cohort of 21 patients (18 probands, 3 LTLE, 17 MTLE and 1 IGE) were screened for LGI1 mutations. Each of the 8 LGI1 exons and the surrounding splice sites were amplified by PCR and sequenced directly. Age at seizure onset ranged from 1 to 52 years (mean 16.5years). Febrile seizures were present in 4 MTLE patients. Simple partial seizures were present in 94.4% of all patients. Autonomic auras, especially epigastric sensation and fear, were the most prevalent auras in the MTLE patients. Auditory auras were present in all 3 LTLE patients and in 4 familial MTLE patients in association with additional mesial symptoms such as experiential phenomena. Complex partial seizures were present in 73.3% of MTLE patients and 66.7% of LTLE patients. 66.7% of both MTLE and LTLE patients had secondary generalized tonic clonic seizures. Refractory seizures were present in more than half of the MTLE patients and in the 2 patients with sporadic LTLE. Imaging detected abnormal mesial structures in 7 patients, with the majority displaying hippocampal atrophy with or without amygdala involvement. EEG demonstrated epileptiform temporal lobe discharges in 13 patients.
No mutations were detected in the coding regions of the LGI1 gene. We did however detect 2 intronic single nucleotide polymorphisms (SNPs) in 3 patients (2 MTLE and 1 LTLE). One is a novel G to C polymorphism 56 base pairs upstream of exon 2. The second is a C to T polymorphism 18 bases upstream of exon 7. To date, we did not find any known or novel LGI1 gene mutations in our preliminary cohort of 21 TLE patients. However, the significance of the two intronic SNPs found in three of our patients requires further investigation. Since LGI1 gene has now been associated with a wider range of epilepsy phenotypes, including idiopathic generalized epilepsy (Ottman et al., 2004), it is possible that SNPs in the intronic regions of the LGI1 gene could be acting as modifying factors leading to phenotypic variability in TLE families. (Supported by EA:Canadian Institutes of Health Research Grant
EK:Preston Robb Fellowship
DD:Savoy Foundation Fellowship)