Article (Scientific journals)
Spectrum of GABAA receptor variants in epilepsy
Maljevic, Snezana; Møller, Rikke S.; Reid, Christopher A. et al.
2019In Current Opinion in Neurology
Peer Reviewed verified by ORBi
 

Files


Full Text
CurOpNeurolgy.Proofs.pdf
Author preprint (557.45 kB)
Request a copy

All documents in ORBilu are protected by a user license.

Send to



Details



Keywords :
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 center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
Disciplines :
Neurology
Genetics & genetic processes
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
External co-authors :
yes
Language :
English
Title :
Spectrum of GABAA receptor variants in epilepsy
Publication date :
16 January 2019
Journal title :
Current Opinion in Neurology
ISSN :
1473-6551
Publisher :
Lippincott Williams & Wilkins, London, United States
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
Available on ORBilu :
since 21 January 2019

Statistics


Number of views
105 (1 by Unilu)
Number of downloads
0 (0 by Unilu)

Scopus citations®
 
50
Scopus citations®
without self-citations
39
WoS citations
 
45

Bibliography


Similar publications



Contact ORBilu