Journal article

Gain-of-function HCN2 variants in genetic epilepsy

Melody Li, Snezana Maljevic, A Marie Phillips, Slave Petrovski, Michael S Hildebrand, Rosemary Burgess, Therese Mount, Federico Zara, Pasquale Striano, Julian Schubert, Holger Thiele, Peter Nuernberg, Michael Wong, Judith L Weisenberg, Liu Lin Thio, Holger Lerche, Ingrid E Scheffer, Samuel F Berkovic, Steven Petrou, Christopher A Reid

HUMAN MUTATION | WILEY | Published : 2018


Genetic generalized epilepsy (GGE) is a common epilepsy syndrome that encompasses seizure disorders characterized by spike-and-wave discharges (SWDs). Pacemaker hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are considered integral to SWD genesis, making them an ideal gene candidate for GGE. We identified HCN2 missense variants from a large cohort of 585 GGE patients, recruited by the Epilepsy Phenome-Genome Project (EPGP), and performed functional analysis using two-electrode voltage clamp recordings from Xenopus oocytes. The p.S632W variant was identified in a patient with idiopathic photosensitive occipital epilepsy and segregated in the family. This variant was also i..

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Awarded by National Health and Medical Research Council of Australia

Awarded by European Commission (Integrated Project Epicure)

Awarded by European Science Foundation Eurocores project EuroEPINOMICS (CoGIE)

Funding Acknowledgements

National Health and Medical Research Council of Australia (10915693, 1005050); European Commission (Integrated Project Epicure, LSH037315); European Science Foundation Eurocores project EuroEPINOMICS (CoGIE) (DFGLe1030/11-1); Dowd Fellowship; Endeavour Research Fellowship of the Australian Government; The Florey Institute of Neuroscience and Mental Health; Victorian Government; Operational Infrastructure Support Grant.