Genomic DNA methylation distinguishes subtypes of human focal cortical dysplasia

Journal article

Publication Details

Author(s): Kobow K, Ziemann M, Kaipananickal H, Khurana I, Mühlebner A, Feucht M, Hainfellner JA, Czech T, Aronica E, Pieper T, Holthausen H, Kudernatsch M, Hamer H, Kasper B, Rössler K, Conti V, Guerrini R, Coras R, Blümcke I, El-Osta A, Kaspi A
Journal: Epilepsia
Publication year: 2019
Volume: 60
Journal issue: 6
Pages range: 1091-1103
ISSN: 0013-9580


Objectives: Focal cortical dysplasia (FCD) is a major cause of drug-resistant focal epilepsy in children, and the clinicopathological classification remains a challenging issue in daily practice. With the recent progress in DNA methylation–based classification of human brain tumors we examined whether genomic DNA methylation and gene expression analysis can be used to also distinguish human FCD subtypes. Methods: DNA methylomes and transcriptomes were generated from massive parallel sequencing in 15 surgical FCD specimens, matched with 5 epilepsy and 6 nonepilepsy controls. Results: Differential hierarchical cluster analysis of DNA methylation distinguished major FCD subtypes (ie, Ia, IIa, and IIb) from patients with temporal lobe epilepsy patients and nonepileptic controls. Targeted panel sequencing identified a novel likely pathogenic variant in DEPDC5 in a patient with FCD type IIa. However, no enrichment of differential DNA methylation or gene expression was observed in mechanistic target of rapamycin (mTOR) pathway–related genes. Significance: Our studies extend the evidence for disease-specific methylation signatures toward focal epilepsies in favor of an integrated clinicopathologic and molecular classification system of FCD subtypes incorporating genomic methylation.

FAU Authors / FAU Editors

Blümcke, Ingmar Prof. Dr.
Lehrstuhl für Neuropathologie
Hamer, Hajo Prof. Dr. med.
Professur für Epileptologie
Kasper, Burkhard Prof. Dr.
Medizinische Fakultät

External institutions with authors

Azienda Ospedaliera Universitaria Meyer
Medizinische Universität Wien
Monash University
Schön Kliniken
University of Amsterdam

How to cite

Kobow, K., Ziemann, M., Kaipananickal, H., Khurana, I., Mühlebner, A., Feucht, M.,... Kaspi, A. (2019). Genomic DNA methylation distinguishes subtypes of human focal cortical dysplasia. Epilepsia, 60(6), 1091-1103.

Kobow, Katja, et al. "Genomic DNA methylation distinguishes subtypes of human focal cortical dysplasia." Epilepsia 60.6 (2019): 1091-1103.


Last updated on 2019-23-07 at 12:38