Spectrum of GABAA receptor variants in epilepsy

Maljevic, Snezana; Møller, Rikke S.; Reid, Christopher A.; Pérez-Palma, Eduardo; Lal, Dennis; May, Patrick; Lerche, Holger

doi:10.1097/WCO.0000000000000657

Reference : Spectrum of GABAA receptor variants in epilepsy


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Genetics & genetic processes Human health sciences : Neurology
	Focus Areas :	Systems Biomedicine
	To cite this reference:	http://hdl.handle.net/10993/38463

Title :	Spectrum of GABAA receptor variants in epilepsy
Language :	English
Author, co-author :	Maljevic, Snezana []
	Møller, Rikke S. []
	Reid, Christopher A. []
	Pérez-Palma, Eduardo []
	Lal, Dennis []
	May, Patrick [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
	Lerche, Holger []
Publication date :	16-Jan-2019
Journal title :	Current Opinion in Neurology
Publisher :	Lippincott Williams & Wilkins
Peer reviewed :	Yes (verified by ORBi^lu)
ISSN :	1350-7540
e-ISSN :	1473-6551
City :	London
Country :	United States
Keywords :	[en] epilepsy ; GABAergic pathway ; Genetics
Abstract :	[en] Purpose of review: Recent publications point to an increasingly important role of variants in genes encoding GABAA receptor subunits associated with both common and rare forms of epilepsies. The aim of this review is to give an overview of the current clinical phenotypes, genetic findings and pathophysiological mechanisms related to GABAA receptor variants. Recent findings: Early work showed that inherited variants in GABRG2 and GABRA1 cause relatively mild forms of monogenic epilepsies in large families. More recent studies have revealed that de novo variants in several GABAA receptor genes cause severe developmental and epileptic encephalopathies, inherited variants cause remarkably variable phenotypes within the same pedigrees ranging from asymptomatic carriers to developmental and epileptic encephalopathies, and variants in all GABAA receptor genes are enriched in common forms of epilepsy, namely rolandic epilepsy and genetic generalized epilepsy. Analyses from cellular expression systems and mouse models suggest that all variants cause a loss of GABAA receptor function resulting in GABAergic disinhibition. Summary: Genetic studies have revealed a crucial role of the GABAergic system in the underlying pathogenesis of various forms of common and rare epilepsies. Our understanding of functional consequences of GABAA receptor variants provide an opportunity to develop precision-based therapeutic strategies that are hopefully free from the side-effect burden seen with currently available GABAergic drugs.
Research centres :	Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
Permalink :	http://hdl.handle.net/10993/38463
DOI :	10.1097/WCO.0000000000000657
Other URL :	https://journals.lww.com/co-neurology/Abstract/publishahead/Spectrum_of_GABAA_receptor_variants_in_epilepsy.99056.aspx

File(s) associated to this reference

Fulltext file(s):

	File	Commentary	Version	Size	Access
Limited access	CurOpNeurolgy.Proofs.pdf		Author preprint	544.38 kB	Request a copy

All documents in ORBi^lu are protected by a user license.

University of Luxembourg Library | Feedback | Legal notices