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Vogel, F.D.* ; Krenn, M.* ; Westphal, D.S.* ; Graf, E.* ; Wagner, M. ; Leiz, S.* ; Koniuszewski, F.* ; Augé-Stock, M.* ; Kramer, G.* ; Scholze, P.* ; Ernst, M.*

A de novo missense variant in GABRA4 alters receptor function in an epileptic and neurodevelopmental phenotype.

Epilepsia 63, e35-e41 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Variants in γ-aminobutyric acid A (GABAA) receptor genes cause different forms of epilepsy and neurodevelopmental disorders. To date, GABRA4, encoding the α4-subunit, has not been associated with a monogenic condition. However, preclinical evidence points toward seizure susceptibility. Here, we report a de novo missense variant in GABRA4 (c.899C>T, p.Thr300Ile) in an individual with early-onset drug-resistant epilepsy and neurodevelopmental abnormalities. An electrophysiological characterization of the variant, which is located in the pore-forming domain, shows accelerated desensitization and a lack of seizure-protective neurosteroid function. In conclusion, our findings strongly suggest an association between de novo variation in GABRA4 and a neurodevelopmental disorder with epilepsy.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Drug-resistant Epilepsy ; Early-onset Epilepsy ; Gaba Receptors A ; Neurosteroid ; Tonic Inhibition ; Trio Exome Sequencing; Gaba(a) Receptors; Epilepsies; Genes
ISSN (print) / ISBN 0013-9580
e-ISSN 1528-1167
Zeitschrift Epilepsia
Quellenangaben Band: 63, Heft: 4, Seiten: e35-e41 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Förderungen Austrian Science Fund