Related Experiment Video
Updated: Aug 26, 2025
Multi-electrode Array Recordings of Human Epileptic Postoperative Cortical Tissue
Published on: October 26, 2014
Somatic Mosaic Pathogenic Variant Gradient Detected in Trace Brain Tissue From Stereo-EEG Depth Electrodes
Zimeng Ye1, Mark F Bennett1, Andrew Neal1
1From the Department of Medicine (Austin Health) (Z.Y., M.F.B., S.K.P., I.E.S., S.F.B., P.P., M.S.H.), University of Melbourne, Heidelberg; Population Health and Immunity Division (M.F.B., M.B.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.F.B., M.B.), The University of Melbourne, Parkville; Department of Neurology (A.N., P.K., T.J.O.B., P.P.), Royal Melbourne Hospital, Parkville; Department of Neurology (A.N., J.A.L., T.W., M.T., P.K., T.J.O.B., P.P.), Alfred Hospital, Melbourne; Department of Medicine (A.N., P.K., T.J.O.B.), Royal Melbourne Hospital, University of Melbourne, Parkville; Department of Neurosciences (A.N., J.A.L., T.W., M.T., P.K., T.J.O.B., P.P.), The Central Clinical School, Monash University, Melbourne; Department of Neurology (A.N.), St Vincent's Hospital, Fitzroy; Department of Neurosurgery (M.K.H.), The Alfred Hospital, Melbourne; Florey Institute of Neuroscience and Mental Health (S.K.P., I.E.S.), Heidelberg; Murdoch Children's Research Institute (I.E.S., M.S.H.), Parkville; Department of Paediatrics (I.E.S.), University of Melbourne, Royal Children's Hospital, Parkville; and Bladin-Berkovic Comprehensive Epilepsy Program (S.F.B., P.P.), Department of Neurology, Austin Health, Heidelberg, Australia.
Researchers identified a mosaic KCNT1 gene variant in brain tissue from epilepsy surgery electrodes. This variant showed a gradient correlating with seizure activity, proving trace tissue analysis is feasible.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Mosaic pathogenic variants in brain DNA are a known cause of focal epilepsies.
- Identifying these variants and their distribution is crucial for understanding epilepsy.
- Stereoelectroencephalography (SEEG) provides localized brain data.
Purpose of the Study:
- To identify a mosaic pathogenic variant and its anatomical gradient in brain DNA.
- To analyze trace tissue from explanted SEEG electrodes for mosaic variants.
- To correlate variant distribution with epilepsy characteristics.
Main Methods:
- Whole genome amplification of trace DNA from SEEG electrodes.
- High-depth exome sequencing to detect variants.
- Droplet digital PCR for mosaicism quantification.
- GFAP assay for cell-of-origin analysis.
Main Results:
- A novel mosaic KCNT1 loss-of-function variant (c.530G>A, p.W177X) was identified.
- A clear mosaic gradient of the variant was observed, correlating with EEG findings.
- Highest variant allele frequency was in the most epileptogenic brain region.
Conclusions:
- Mosaic gradients of pathogenic variants can be detected using trace tissue from explanted SEEG electrodes.
- This method offers a proof of concept for analyzing localized brain mosaicism.
- Establishes a novel approach for epilepsy research and diagnostics.
More Related Videos
11:00Reliable Acquisition of Electroencephalography Data during Simultaneous Electroencephalography and Functional MRI
Published on: March 19, 2021
13:12Translational Brain Mapping at the University of Rochester Medical Center: Preserving the Mind Through Personalized Brain Mapping
Published on: August 12, 2019