Recurrent SLC1A2 variants cause epilepsy via a dominant negative mechanism.

DOI
Publisher DOI
PubMed ID
30937933
Abstract
SLC1A2 is a trimeric transporter essential for clearing glutamate from neuronal synapses. Recurrent de novo SLC1A2 missense variants cause a severe, early-onset developmental and epileptic encephalopathy via an unclear mechanism. We demonstrate that all three variants implicated in this condition localize to the trimerization domain of SLC1A2, and that the Leu85Pro variant acts via a dominant negative mechanism to reduce, but not eliminate, wild-type SLC1A2 protein localization and function. Finally, we demonstrate that treatment of a 20-month-old SLC1A2-related epilepsy patient with the SLC1A2 modulating agent ceftriaxone did not result in a significant change in daily spasm count. This article is protected by copyright. All rights reserved.
Date Issued
2019-04-01
Publication Type
Article
Subject(s)
Subjects
Epilepsy Neurogenetics SLC1A2
Language(s)
en
Author(s)
Stergachis, Andrew B
Gyimesi, Gergely
Troxler, Marina
Picker, Jonathan
Rosenberg, Paul A
Bergin, Ann
Peters, Jurriaan
Moufawad El Achkar, Christelle
Harini, Chellamani
Manzi, Shannon
Rotenberg, Alexander
Rodan, Lance H
Additional Credits
Journal
Annals of neurology
Publisher
Wiley-Blackwell
ISSN
0364-5134
Access(Rights)
restricted
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