Abstracts

Rationale: Recently, we identified a locus for familial mesial temporal lobe epilepsy (MTLE) associated with hippocampal atrophy on chromosome 18p. Among several genes localized within the candidate interval of 6 cM is PTPRM, a gene that is highly expressed in hippocampus. The aim of this study was to investigate PTPRM gene expression in tissue samples from familial and sporadic (non-familial) MTLE patients who underwent surgery for medically refractory seizures. Methods: Patients that underwent surgery had a complete clinical, EEG and imaging investigation as part of the clinical protocol for epilepsy surgery in our University Hospital. We selected eight specimens obtained from epilepsy surgery and four samples from autopsy (control group). The specimens (control n=4, sporadic MTLE n=4 and familial MTLE n=4) were immediately frozen after resection and stored at -80oC. We obtained RNA from samples by standard protocols using TRIzol. We used 8ng of the cDNA to perform quantitative real time PCR using the TaqMan® gene expression assay. Experiments were performed in triplicate and an internal control was used to unsure quality control (18S) in all assays. We used one-way ANOVA with Tukey post hoc comparison test to analyze the data. Results: Presurgical evaluation of all patients indicated MTLE, including MRI evidence of unilateral hippocampal atrophy. The mean relative gene expression and standard error (SEM) for each group was: control: 0.83 ± 0.1; familial MTLE: 0.78 ± 0.05 and sporadic MTLE: 2.29 ± 0.25. Comparison among groups showed that PTPRM is differentially expressed only in the sporadic MTLE group (p<0.001). No significant difference between familial MTLE and the control group was observed (P>0.05). Conclusions: We found a significant increase in PTPRM gene expression in surgical specimens obtained from patients with sporadic MTLE indicating that PTPRM may play a role in the pathophysiology of MTLE in this group of patients. These results indicate that gene expression profile maybe different in familial and sporadic MTLE. Support: FAPESP and CNPq.