Abstracts

Rationale: Cortical malformations of development (cortical tubers; CT) in patients with the tuberous sclerosis complex (TSC) are associated with intractable epilepsy, the most common neurological symptom in TSC. The molecular mechanisms of the development of CT is to a certain extent established, however the mechanisms underlying the epileptogenicity remains largely unknown. Methods: Using the Affymetrix Gene Chip System we studied the gene expression profile of CT in comparison with autopsy control specimens and perituberal tissue (adjacent to the CT) from the same patients. Differentially expressed genes were classified according to the Gene Ontology (GO) system. Results: We identified multiple genes, processes and pathways that were differentially expressed in CT compared to control material. Genes linked to cell adhesion, such as VCAM, Integrins and CD44, had a higher expression level in CT specimens. Higher expression levels were also observed for genes related to apoptosis and the immune and inflammatory response, including complement factors. The expression of genes related to synaptic transmission, ubiquitination and voltage-gated channel activity was lower in CT, compared to control material. Signaling pathways linked to the differentially expressed genes included the integrin signaling pathway, the mammalian target of rapamycin (mTOR) signaling pathway, cell death associated signaling pathways and the complement pathway. Conclusions: These data provide insights in the molecular mechanisms present in cortical tuber specimens and offers suggestions for both the pathogenesis and epileptogenesis of these developmental lesions.