Mos-FED (Mosaicism in Focal Epilepsy Cortical Dysplasia Tissue)

Overview

Focal cortical dysplasia (FCD) is a malformation of brain development, the most common cause of drug-resistant epilepsy and often caused by mutations in mammalian target of rapamycin (mTOR) pathway genes. Patients with FCD develop drug-resistant seizures. This study will look at FCD tissue removed during epilepsy surgery and aims to detect mutations in mTOR pathway genes in brain cells. Secondly, the investigators will establish if evidence of mutations found in brain cells can also be detected as circulating free DNA (cfDNA) in blood. By looking at which genes are made into proteins in individual cells found in epilepsy surgical tissue (single cell expression profiling),the investigators will attempt to identify new genetic targets in FCD. The main outcome will be finding new causes of epilepsy with FCD and the development of new diagnostic and screening tools.

Primary Objectives: 1. To identify if somatic mosaicism for mTOR is present in resected tissue from patients with FCDIIA/B, and can be detected in DNA from patient's serum as circulating free DNA (cfDNA) or from nasal epithelial cells collected non-invasively by olfactory mucosal brush swab. 2. To establish if single cell expression profiling from resected fresh frozen tissue reveals novel FCD causing pathways and single cell RNA sequencing increases the yield of mTOR pathway variant detection. 3. To determine if phosphorylated upstream and downstream mTOR pathway components can be characterised by immunohistochemistry and Western blot as novel biomarkers of mTOR activation in human FCDII tissue. Secondary Objectives: To engage with patients, representatives and charitable organisations to assess feasibility and develop plan to set up a future trial of mTOR inhibitor treatment.