Reference : Assessment of genetic variant burden in epilepsy-associated brain lesions
Scientific journals : Article
Life sciences : Genetics & genetic processes
Systems Biomedicine
http://hdl.handle.net/10993/40002
Assessment of genetic variant burden in epilepsy-associated brain lesions
English
Niestroj, Lisa-Marie []
May, Patrick mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Artomov, Mykyta []
Kobow, Katja []
Coras, Roland []
Pérez-Palma, Eduardo []
Altmüller, Janine []
Thiele, Holger []
Nürnberg, Peter []
Leu, Costin []
Palotie, Aarno []
Daly, Mark J. []
Klein, Karl-Martin []
Beschorner, Rudi []
Weber, Yvonne G. []
Blümcke, Ingmar []
Lal, Dennis []
29-Jul-2019
European Journal of Human Genetics
Natue Publishing Group
Yes
International
1018-4813
1476-5438
London
United Kingdom
[en] Neuropathologies ; Focal cortical dysplasia ; Hippocampal sclerosis ; Low-grade 24 epilepsy associated tumors ; Variant burden ; Focal epilepsy
[en] It is challenging to estimate genetic variant burden across different subtypes of epilepsy. Herein, we used a comparative approach to assess the diagnostic yield and genotype-phenotype correlations in the four most common brain lesions in patients with drug-resistant focal epilepsy. Targeted sequencing analysis was performed for a panel of 161 genes with a mean coverage of > 400x. Lesional tissue was histopathologically reviewed and dissected from hippocampal sclerosis (n=15), ganglioglioma (n=16), dysembryoplastic neuroepithelial tumors (n=8) and ocal cortical dysplasia type II (n=15). Peripheral blood (n=12) or surgical tissue samples histopathologically classified as lesion-free (n=42) were available for comparison. Variants were classified as pathogenic or likely pathogenic according to American College of Medical Genetics and Genomics guidelines. Overall, we identified pathogenic and likely pathogenic variants in 25.9% of patients with a mean coverage of 383x. The highest number of pathogenic/ likely pathogenic variants was observed in patients with ganglioglioma (43.75%; all somatic) and dysembryoplastic neuroepithelial tumors (37.5%; all somatic), and in 20% of cases with focal cortical dysplasia type II (13.33% somatic, 6.67% germline). Pathogenic/likely pathogenic positive genes were disorder-specific and BRAF V600E the only recurrent pathogenic variant. This study represents a reference for diagnostic yield across the four most common lesion entities in patients with drug-resistant focal epilepsy. The observed large variability in variant burden by epileptic lesion type calls for whole exome sequencing of histopathologically well characterized tissue in a diagnostic setting and in research to discover novel disease-associated genes.
Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
Researchers
http://hdl.handle.net/10993/40002
10.1038/s41431-019-0484-4
https://www.nature.com/articles/s41431-019-0484-4

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Limited access
Niestroj2019.EJHG.pdfPublisher postprint896.95 kBRequest a copy

Bookmark and Share SFX Query

All documents in ORBilu are protected by a user license.