Recurrent SLC1A2 variants cause epilepsy via a dominant negative mechanism.
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ABSTRACT:
SUBMITTER: Stergachis AB
PROVIDER: S-EPMC6800210 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
Publications
Recurrent SLC1A2 variants cause epilepsy via a dominant negative mechanism.
Stergachis Andrew B AB Pujol-Giménez Jonai J Gyimesi Gergely G Fuster Daniel D Albano Giusppe G Troxler Marina M Picker Jonathan J Rosenberg Paul A PA Bergin Ann A Peters Jurriaan J El Achkar Christelle Moufawad CM Harini Chellamani C Manzi Shannon S Rotenberg Alexander A Hediger Matthias A MA Rodan Lance H LH
Annals of neurology 20190426 6
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 3 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 ...[more]
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