Cutting edge approaches to detecting brain mosaicism associated with common focal epilepsies: implications for diagnosis and potential therapies

doi:10.1080/14737175.2021.1981288

. 2021 Nov;21(11):1309-1316.

doi: 10.1080/14737175.2021.1981288. Epub 2021 Sep 22.

Cutting edge approaches to detecting brain mosaicism associated with common focal epilepsies: implications for diagnosis and potential therapies

Zimeng Ye¹, Mark F Bennett^{1

2

3}, Melanie Bahlo^{2

3}, Ingrid E Scheffer^{1

4

5

6}, Samuel F Berkovic^{1

6}, Piero Perucca^{1

6

7

8

9}, Michael S Hildebrand^{1

4}

Affiliations

¹ Department of Medicine (Austin Health), Epilepsy Research Centre, University of Melbourne, Heidelberg, Australia.
² Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
³ Department of Medical Biology, The University of Melbourne, Parkville, Australia.
⁴ Neuroscience Research Group, Murdoch Children's Research Institute, Parkville, Australia.
⁵ Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Australia.
⁶ Department of Neurology, Comprehensive Epilepsy Program, Austin Health, Heidelberg, Australia.
⁷ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia.
⁸ Department of Neurology, Alfred Health, Melbourne, Australia.
⁹ Department of Neurology, The Royal Melbourne Hospital, Parkville, Australia.

PMID: 34519595
DOI: 10.1080/14737175.2021.1981288

Cutting edge approaches to detecting brain mosaicism associated with common focal epilepsies: implications for diagnosis and potential therapies

Zimeng Ye et al. Expert Rev Neurother. 2021 Nov.

. 2021 Nov;21(11):1309-1316.

doi: 10.1080/14737175.2021.1981288. Epub 2021 Sep 22.

Authors

Zimeng Ye¹, Mark F Bennett^{1

2

3}, Melanie Bahlo^{2

3}, Ingrid E Scheffer^{1

4

5

6}, Samuel F Berkovic^{1

6}, Piero Perucca^{1

6

7

8

9}, Michael S Hildebrand^{1

4}

Affiliations

¹ Department of Medicine (Austin Health), Epilepsy Research Centre, University of Melbourne, Heidelberg, Australia.
² Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
³ Department of Medical Biology, The University of Melbourne, Parkville, Australia.
⁴ Neuroscience Research Group, Murdoch Children's Research Institute, Parkville, Australia.
⁵ Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Australia.
⁶ Department of Neurology, Comprehensive Epilepsy Program, Austin Health, Heidelberg, Australia.
⁷ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia.
⁸ Department of Neurology, Alfred Health, Melbourne, Australia.
⁹ Department of Neurology, The Royal Melbourne Hospital, Parkville, Australia.

PMID: 34519595
DOI: 10.1080/14737175.2021.1981288

Abstract

Introduction: Mosaic variants arising in brain tissue are increasingly being recognized as a hidden cause of focal epilepsy. This knowledge gain has been driven by new, highly sensitive genetic technologies and genome-wide analysis of brain tissue from surgical resection or autopsy in a small proportion of patients with focal epilepsy. Recently reported novel strategies to detect mosaic variants limited to brain have exploited trace brain DNA obtained from cerebrospinal fluid liquid biopsies or stereo-electroencephalography electrodes.

Areas covered: The authors review the data on these innovative approaches published in PubMed before 12 June 2021, discuss the challenges associated with their application, and describe how they are likely to improve detection of mosaic variants to provide new molecular diagnoses and therapeutic targets for focal epilepsy, with potential utility in other nonmalignant neurological disorders.

Expert opinion: These cutting-edge approaches may reveal the hidden genetic etiology of focal epilepsies and provide guidance for precision medicine.

Keywords: Brain lesion; CSF liquid biopsy; focal epilepsy; high-depth exome sequencing; somatic mosaicism; stereo-electroencephalography.

PubMed Disclaimer

Cited by

Analysis of DNA from brain tissue on stereo-EEG electrodes reveals mosaic epilepsy-related variants.
D'Gama AM, Phillips HW, Wang Y, Chiu MY, Chahine Y, Swanson AC, Smith RS, Pearl PL, Tsuboyama M, Madsen JR, Lidov H, Lee EA, Prabhu SP, Huang AY, Stone SSD, Walsh CA, Poduri A. D'Gama AM, et al. Brain Commun. 2025 Mar 17;7(2):fcaf113. doi: 10.1093/braincomms/fcaf113. eCollection 2025. Brain Commun. 2025. PMID: 40177531 Free PMC article.

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Atypon

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Cutting edge approaches to detecting brain mosaicism associated with common focal epilepsies: implications for diagnosis and potential therapies

Affiliations

Cutting edge approaches to detecting brain mosaicism associated with common focal epilepsies: implications for diagnosis and potential therapies

Authors

Affiliations

Abstract

Similar articles

Cited by

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Abstract

Similar articles

Cited by

Publication types

MeSH terms

Related information

LinkOut - more resources

Full Text Sources