Detection of brain somatic mutations in focal cortical dysplasia during epilepsy presurgical workup.
Rayann ChecriMathilde ChipauxSarah Ferrand-SorbetsEmmanuel RaffoChristine BulteauSarah Dominique RosenbergMarion DoladilheGeorg DorfmüllerHoma Adle-BiassetteSara BaldassariStephanie BaulacPublished in: Brain communications (2023)
Brain-restricted somatic variants in genes of the mechanistic target of rapamycin signalling pathway cause focal epilepsies associated with focal cortical dysplasia type II. We hypothesized that somatic variants could be identified from trace tissue adherent to explanted stereoelectroencephalography electrodes used in the presurgical epilepsy workup to localize the epileptogenic zone. We investigated three paediatric patients with drug-resistant focal epilepsy subjected to neurosurgery. In the resected brain tissue, we identified low-level mosaic somatic mutations in AKT3 and DEPDC5 genes. We collected stereoelectroencephalography depth electrodes in the context of a second presurgical evaluation and identified 4/33 mutation-positive electrodes that were either located in the epileptogenic zone or at the border of the dysplasia. We provide the proof-of-concept that somatic mutations with low levels of mosaicism can be detected from individual stereoelectroencephalography electrodes and support a link between the mutation load and the epileptic activity. Our findings emphasize future opportunities for integrating genetic testing from stereoelectroencephalography electrodes into the presurgical evaluation of refractory epilepsy patients with focal cortical dysplasia type II to improve the patients' diagnostic journey and guide towards precision medicine.
Keyphrases
- copy number
- drug resistant
- genome wide
- reduced graphene oxide
- solid state
- white matter
- resting state
- carbon nanotubes
- multidrug resistant
- end stage renal disease
- prognostic factors
- acinetobacter baumannii
- ejection fraction
- emergency department
- cerebral ischemia
- signaling pathway
- intensive care unit
- multiple sclerosis
- heavy metals
- cell proliferation
- functional connectivity
- risk assessment
- cystic fibrosis
- gold nanoparticles
- temporal lobe epilepsy
- optical coherence tomography
- blood brain barrier
- single molecule
- quantum dots
- transcription factor
- real time pcr
- mass spectrometry