Reference : Targeted sequencing of 351 candidate genes for epileptic encephalopathy in a large co...

	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Genetics & genetic processes
	Focus Areas :	Systems Biomedicine
	To cite this reference:	http://hdl.handle.net/10993/30298

Title :	Targeted sequencing of 351 candidate genes for epileptic encephalopathy in a large cohort of patients
Language :	English
Author, co-author :	de Kovel, Carolien G.F. [> >]
	Brilstra, Eva H. [> >]
	van Kempen J.A. [> >]
	van't Slot, Ruben [> >]
	Nijman, Isaac J. [> >]
	Afawi, Zaid [> >]
	De Jonghe, Peter [> >]
	Djemie, Tania [> >]
	Guerrini, Renzo [> >]
	Hardies, Katia [> >]
	Helbig, Ingo [> >]
	Hendrickx, Rik [> >]
	Kanaan, Moine [> >]
	Kramer, Uri [> >]
	Lehesjoki, Anna-Elina E. [> >]
	Lemke, Johannes R. [> >]
	Marini, Carla [> >]
	Mei, Davide [> >]
	Moller, Rikke S. [> >]
	Pendziwiat, Manuela [> >]
	Stamberger, Hannah [> >]
	Suls, Arvid [> >]
	Weckhuysen, Sarah [> >]
	EuroEPINOMICS RES Consortium [> >]
	May, Patrick [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
	Balling, Rudi [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
	Koeleman, Bobby P.C. [> >]
Publication date :	30-Jul-2016
Journal title :	Molecular Genetics and Genomic Medicine
Volume :	4
Issue/season :	5
Pages :	568-80
Peer reviewed :	Yes
Audience :	International
Keywords :	[en] Genetics ; Epilepsy ; Genomics
Abstract :	[en] Background Many genes are candidates for involvement in epileptic encephalopathy (EE) because one or a few possibly pathogenic variants have been found in patients, but insufficient genetic or functional evidence exists for a definite annotation. Methods To increase the number of validated EE genes, we sequenced 26 known and 351 candidate genes for EE in 360 patients. Variants in 25 genes known to be involved in EE or related phenotypes were followed up in 41 patients. We prioritized the candidate genes, and followed up 31 variants in this prioritized subset of candidate genes. Results Twenty-nine genotypes in known genes for EE (19) or related diseases (10), dominant as well as recessive or X-linked, were classified as likely pathogenic variants. Among those, likely pathogenic de novo variants were found in EE genes that act dominantly, including the recently identified genes EEF1A2, KCNB1 and the X-linked gene IQSEC2. A de novo frameshift variant in candidate gene HNRNPU was the only de novo variant found among the followed-up candidate genes, and the patient's phenotype was similar to a few recent publications. Conclusion Mutations in genes described in OMIM as, for example, intellectual disability gene can lead to phenotypes that get classified as EE in the clinic. We confirmed existing literature reports that de novo loss-of-function HNRNPUmutations lead to severe developmental delay and febrile seizures in the first year of life.
Research centres :	Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group)
Permalink :	http://hdl.handle.net/10993/30298
DOI :	10.1002/mgg3.235
Other URL :	http://onlinelibrary.wiley.com.proxy.bnl.lu/doi/10.1002/mgg3.235/abstract

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