Epilepsies are one of the most frequent neurological diseases, affecting 1.5 -2% of the worldwide population. Malformations of cortical development (MCD), including Focal Cortical Dysplasia (FCD), can cause epilepsy and are often associated with the occurrence of refractory seizures. FCD is characterized by alterations in cytoarchitecture also observed in other MDCs, such as in Tuberous Sclerosis (ET) and Hemimegaencefalia (HME). Recently, an association among mosaic mutations, ET and HME has been reported. The identification of mosaic mutations can contribute to the understanding of complex diseases, however this class of variants is not usually detected by Sanger sequencing. Thus, the possibility of identify somatic mutations by the next generation sequencing techniques (NGS) represents a new approach in the study of neurological diseases. Therefore, the main objective of this project is to investigate whether mosaic mutations are associated with FCD. We are going to use a Deep Sequencing strategy. Genomic DNA from brain tissue resected by surgery and peripheral blood of patients with FCD will be sequenced to assess whether mosaicism is restricted to the central nervous system. We will perform capture and enrichment with Nextera® Expanded Kit (Illumina®), and samples will be sequenced in a Hiseq2500 (Illumina®). In addition, Copy Number Variations (CNVs) will be investigated using CytoScanHD (Affymetrix). We hope that this project will contribute to a better understanding of the genetic etiology of DCFs as well as to identify molecular mechanisms involved in the developing of cerebral cortex.
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