Journal article

SCN1A gain of function in early infantile encephalopathy

Geza Berecki, Alexander Bryson, Jan Terhag, Snezana Maljevic, Elena Gazina, Sean L Hill, Steven Petrou

ANNALS OF NEUROLOGY | WILEY | Published : 2019

Abstract

OBJECTIVE: To elucidate the biophysical basis underlying the distinct and severe clinical presentation in patients with the recurrent missense SCN1A variant, p.Thr226Met. Patients with this variant show a well-defined genotype-phenotype correlation and present with developmental and early infantile epileptic encephalopathy that is far more severe than typical SCN1A Dravet syndrome. METHODS: Whole cell patch clamp and dynamic action potential clamp were used to study T226M Nav 1.1 channels expressed in mammalian cells. Computational modeling was used to explore the neuronal scale mechanisms that account for altered action potential firing. RESULTS: T226M channels exhibited hyperpolarizing shi..

View full abstract

Grants

Awarded by Australian Research Council Centre of Excellence for Integrative Brain Function grant


Awarded by National Health and Medical Research Council (NHMRC) program grant


Awarded by NHMRC fellowship


Funding Acknowledgements

This study was supported by an Australian Research Council Centre of Excellence for Integrative Brain Function grant (CE14010007), a National Health and Medical Research Council (NHMRC) program grant (10915693), and an NHMRC fellowship (GNT1005050) to S.P. This work was also supported by funding from the Eidgenossische Technische Hochschule (ETH) domain for the Blue Brain Project. The Florey Institute of Neuroscience and Mental Health is supported by Victorian State Government infrastructure funds.