Somatic Mosaic Mutation Gradient Detected in Trace Brain Tissue From Stereo-EEG Depth Electrodes.
Journal
Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060
Informations de publication
Date de publication:
03 Oct 2022
03 Oct 2022
Historique:
received:
16
03
2022
accepted:
09
09
2022
entrez:
3
10
2022
pubmed:
4
10
2022
medline:
4
10
2022
Statut:
aheadofprint
Résumé
Mosaic pathogenic variants restricted to brain are increasingly recognized as a cause of focal epilepsies. We aimed to identify a mosaic pathogenic variant and its anatomical gradient in brain DNA derived from trace tissue on explanted stereo-electroencephalography (SEEG) electrodes. We studied a patient with non-lesional multifocal epilepsy undergoing pre-surgical evaluation with SEEG. Following explantation, electrodes were divided into 3 pools based on their brain location (right posterior quadrant, left posterior quadrant, hippocampus/temporal neocortex). Tissue from each pool was processed and DNA whole genome amplified prior to high-depth exome sequencing. Droplet digital PCR was performed to quantify mosaicism. Brain-specific GFAP protein assay enabled cell-of-origin analysis. We demonstrated a mosaic gradient for a novel pathogenic This study demonstrates proof-of-concept that mosaic gradients of pathogenic variants can be established using trace tissue from explanted SEEG electrodes.
Sections du résumé
BACKGROUND AND OBJECTIVES
OBJECTIVE
Mosaic pathogenic variants restricted to brain are increasingly recognized as a cause of focal epilepsies. We aimed to identify a mosaic pathogenic variant and its anatomical gradient in brain DNA derived from trace tissue on explanted stereo-electroencephalography (SEEG) electrodes.
MATERIAL AND METHODS
METHODS
We studied a patient with non-lesional multifocal epilepsy undergoing pre-surgical evaluation with SEEG. Following explantation, electrodes were divided into 3 pools based on their brain location (right posterior quadrant, left posterior quadrant, hippocampus/temporal neocortex). Tissue from each pool was processed and DNA whole genome amplified prior to high-depth exome sequencing. Droplet digital PCR was performed to quantify mosaicism. Brain-specific GFAP protein assay enabled cell-of-origin analysis.
RESULTS
RESULTS
We demonstrated a mosaic gradient for a novel pathogenic
CONCLUSIONS
CONCLUSIONS
This study demonstrates proof-of-concept that mosaic gradients of pathogenic variants can be established using trace tissue from explanted SEEG electrodes.
Identifiants
pubmed: 36192176
pii: WNL.0000000000201469
doi: 10.1212/WNL.0000000000201469
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022 American Academy of Neurology.