Universität zu Köln

Niestroj, Lisa-Marie, May, Patrick ORCID: 0000-0001-8698-3770, Artomov, Mykyta ORCID: 0000-0001-5282-8764, Kobow, Katja ORCID: 0000-0002-0074-2480, Coras, Roland, Perez-Palma, Eduardo ORCID: 0000-0003-0546-5141, Altmueller, Janine, Thiele, Holger, Nuernberg, Peter, Leu, Costin, Palotie, Aarno, Daly, Mark J., Klein, Karl Martin ORCID: 0000-0002-6654-1665, Beschorner, Rudi, Weber, Yvonne G., Bluemcke, Ingmar and Lal, Dennis (2019). Assessment of genetic variant burden in epilepsy-associated brain lesions. Eur. J. Hum. Genet., 27 (11). S. 1738 - 1745. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5438

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Abstract

It is challenging to estimate genetic variant burden across different subtypes of epilepsy. Herein, we used a comparative approach to assess the genetic variant burden and genotype-phenotype correlations in 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 focal 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 the genetic variant burden 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Niestroj, Lisa-Marie UNSPECIFIED UNSPECIFIED UNSPECIFIED May, Patrick UNSPECIFIED orcid.org/0000-0001-8698-3770 UNSPECIFIED Artomov, Mykyta UNSPECIFIED orcid.org/0000-0001-5282-8764 UNSPECIFIED Kobow, Katja UNSPECIFIED orcid.org/0000-0002-0074-2480 UNSPECIFIED Coras, Roland UNSPECIFIED UNSPECIFIED UNSPECIFIED Perez-Palma, Eduardo UNSPECIFIED orcid.org/0000-0003-0546-5141 UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Leu, Costin UNSPECIFIED UNSPECIFIED UNSPECIFIED Palotie, Aarno UNSPECIFIED UNSPECIFIED UNSPECIFIED Daly, Mark J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Karl Martin UNSPECIFIED orcid.org/0000-0002-6654-1665 UNSPECIFIED Beschorner, Rudi UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Yvonne G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bluemcke, Ingmar UNSPECIFIED UNSPECIFIED UNSPECIFIED Lal, Dennis UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-129920
DOI:	10.1038/s41431-019-0484-4
Journal or Publication Title:	Eur. J. Hum. Genet.
Volume:	27
Number:	11
Page Range:	S. 1738 - 1745
Date:	2019
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1476-5438
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FOCAL CORTICAL DYSPLASIA; NEUROEPITHELIAL TUMORS; CONSENSUS CLASSIFICATION; SOMATIC MUTATIONS; ARRAY ANALYSIS; MTOR PATHWAY; TASK-FORCE; GANGLIOGLIOMAS; FGFR1; SCLEROSIS Multiple languages Biochemistry & Molecular Biology; Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12992