Scerif, F; (2016) Identification of gene networks in childhood epilepsy: evidence from focal cortical dysplasia. Doctoral thesis , UCL (University College London).

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Abstract

Introduction: Focal cortical dysplasia (FCD) is a malformation of cortical development that is a frequent cause of multidrug resistant paediatric epilepsy. FCD type IIb (FCDIIb) is characterised by a population of unique abnormally enlarged cells known as balloon cells (BCs). The understanding of the molecular abnormalities underlying FCDIIb is poor. It is unclear if BCs are the key pathological cell or if there are other types of cells that are important in the pathogenesis of the disease. Interactions between such cell types are also unknown. Methods: Bioinformatic analyses of gene expression data were used to identify networks of genes that could characterise FCD and to identify putative diagnostic biomarkers. These markers were validated at the protein level by immunohistochemistry. Furthermore, various techniques allowed for the investigation of possible signalling between different cell types in FCDIIb. Results: Several of the gene networks and biomarkers were differentially expressed between FCDIIb and control. Analysis of one particular network showed that some components were expressed in BCs but others were expressed in a potentially novel cell population that was only present in FCDIIb. The importance of cellular heterogeneity of FCDIIb was further supported by the finding that BCs may have a unique senescence-associated secretome that could be involved in cell-to-cell communications. Conclusion: A genomic characterisation of FCD has provided a better understanding of the cellular abnormalities in FCDIIb from a molecular perspective. In addition to the identification of several differentially expressed gene networks, the results also provide an interesting insight into cell-to-cell communications between different cell types in FCDIIb, which could be important in driving the pathogenesis of the disease.

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