Abstracts

Rationale: MiRNAs are small noncoding RNAs which regulate post-transcriptional gene expression. Focal cortical dysplasia (FCD) is a malformation of cortical development which affects up to 36% of patients with drug-resistant epilepsy. Our goal is to investigate differences in microRNA (miRNAs) regulation in FCDs. Methods: We used brain tissue obtained after surgery for the treatment of medically refractory seizures from nine patients with FCD (four patients with FCD type IIa and five patients with FCD type IIb). In addition, we used cortical tissue from autopsy as controls (n=5). Total RNA was isolated with RecoverAllTM kit (Ambion) and RNA integrity was assessed by Agilent RNA Pico Chip Kit and Bio-Analyzer 2100.MiRNA expression profile was assessed by Affymetrix GeneChip platform miRNA array. Background correction, summarization and normalization were performed by RMA function. MiRNA expression was analyzed using RankProd (p < 0.05). Results: We identified 23 miRNAs with significant different expression when patients and control group were compared. Furthermore, when FCD type IIa and FCD type IIb groups were compared we found six differentially expressed miRNA types. Among them, we observed a significant down-regulation of several elements belonging to the miR-17~92 cluster. This cluster is known to contribute to transcriptional regulation of stem cell differentiation, aging, as well as fine-tuning of pathways involved in neuronal differentiation. Conclusions: Our results clearly show that neurodevelopment pathways are indeed involved in the pathophysiology of FCD. In addition, we identified a different miRNA expression signature in different FCD subtypes which may contribute to improve classification.