Universität zu Köln

Maljevic, Snezana ORCID: 0000-0003-1876-5872, Moller, Rikke S., Reid, Christopher A., Perez-Palma, Eduardo ORCID: 0000-0003-0546-5141, Lal, Dennis, May, Patrick ORCID: 0000-0001-8698-3770 and Lerche, Holger (2019). Spectrum of GABA(A) receptor variants in epilepsy. Curr. Opin. Neurol., 32 (2). S. 183 - 191. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1473-6551

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Abstract

Purpose of review Recent publications point to an increasingly important role of variants in genes encoding GABA(A) 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 GABA(A) 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 GABA(A) 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 GABA(A) 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 GABA(A) 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 GABA(A) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Maljevic, Snezana UNSPECIFIED orcid.org/0000-0003-1876-5872 UNSPECIFIED Moller, Rikke S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reid, Christopher A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Perez-Palma, Eduardo UNSPECIFIED orcid.org/0000-0003-0546-5141 UNSPECIFIED Lal, Dennis UNSPECIFIED UNSPECIFIED UNSPECIFIED May, Patrick UNSPECIFIED orcid.org/0000-0001-8698-3770 UNSPECIFIED Lerche, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-151319
DOI:	10.1097/WCO.0000000000000657
Journal or Publication Title:	Curr. Opin. Neurol.
Volume:	32
Number:	2
Page Range:	S. 183 - 191
Date:	2019
Publisher:	LIPPINCOTT WILLIAMS & WILKINS
Place of Publication:	PHILADELPHIA
ISSN:	1473-6551
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENERALIZED EPILEPSIES; PHENOTYPIC SPECTRUM; CORTICAL INHIBITION; ABSENCE EPILEPSY; MOUSE MODELS; MUTATION; SUBUNIT; GABRA1; PROTEIN; GENES Multiple languages Clinical Neurology; Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15131