How gene mutations cause epilepsy

Antisense oligonucleotide therapy for KCNT1 encephalopathy

Lisseth Estefania Burbano, Melody Li, Nikola Jancovski, Paymaan Jafar-Nejad, Kay Richards, Alicia Sedo, Armand Soriano, Ben Rollo, Linghan Jia, Elena V. Gazina, Sandra Piltz, Fatwa Adikusuma, Paul Q Thomas, Helen Kopsidas, Frank Rigo, Christopher A Reid, Snezana Maljevic, Steven Petrou

2022-12-08

Developmental and epileptic encephalopathies (DEEs) are characterized by pharmaco-resistant seizures with concomitant intellectual..

Antisense oligonucleotide therapy reduces seizures and extends life span in an SCN2A gain-of-function epilepsy model

Melody Li, Nikola Jancovski, Paymaan Jafar-Nejad, Lisseth E Burbano, Ben Rollo, Kay Richards, Lisa Drew, Alicia Sedo, Jacqueline Heighway, Svenja Pachernegg, Armand Soriano, Linghan Jia, Todd Blackburn, Blaine Roberts, Alex Nemiroff, Kelley Dalby, Snezana Maljevic, Christopher A Reid, Frank Rigo, Steven Petrou

2021-12-01

De novo variation in SCN2A can give rise to severe childhood disorders. Biophysical gain of function in SCN2A is seen in some pati..

Novel MissenseCACNA1GMutations Associated with Infantile-Onset Developmental and Epileptic Encephalopathy

Geza Berecki, Katherine L Helbig, Tyson L Ware, Bronwyn Grinton, Cara M Skraban, Eric D Marsh, Samuel F Berkovic, Steven Petrou

2020-09-01

The CACNA1G gene encodes the low-voltage-activated Cav3.1 channel, which is expressed in various areas of the CNS, including the c..

Estimating neuronal conductance model parameters using dynamic action potential clamp

Y Deerasooriya, G Berecki, D Kaplan, IC Forster, S Halgamuge, S Petrou

2019-09-01

Parameterization of neuronal membrane conductance models relies on data acquired from current clamp (CC) or voltage clamp (VC) rec..

SCN1A gain of function in early infantile encephalopathy

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

2019-04-01

OBJECTIVE: To elucidate the biophysical basis underlying the distinct and severe clinical presentation in patients with the recurr..

Dynamic action potential clamp predicts functional separation in mild familial and severe de novo forms of SCN2A epilepsy

Geza Berecki, Katherine B Howell, Yadeesha H Deerasooriya, Maria Roberta Cilio, Megan K Oliva, David Kaplan, Ingrid E Scheffer, Samuel F Berkovic, Steven Petrou

2018-06-12

De novo variants in SCN2A developmental and epileptic encephalopathy (DEE) show distinctive genotype-phenotype correlations. The t..

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

2018-02-01

Genetic generalized epilepsy (GGE) is a common epilepsy syndrome that encompasses seizure disorders characterized by spike-and-wav..

Non-Neurotoxic Nanodiamond Probes for Intraneuronal Temperature Mapping

David A Simpson, Emma Morrisroe, Julia M McCoey, Alain H Lombard, Dulini C Mendis, Francois Treussart, Liam T Hall, Steven Petrou, Lloyd CL Hollenberg

2017-12-01

Optical biomarkers have been used extensively for intracellular imaging with high spatial and temporal resolution. Extending the m..

Models for discovery of targeted therapy in genetic epileptic encephalopathies

Snezana Maljevic, Christopher A Reid, Steven Petrou

2017-10-01

Epileptic encephalopathies are severe disorders emerging in the first days to years of life that commonly include refractory seizu..

Electron paramagnetic resonance microscopy using spins in diamond under ambient conditions

David A Simpson, Robert G Ryan, Liam T Hall, Evgeniy Panchenko, Simon C Drew, Steven Petrou, Paul S Donnelly, Paul Mulvaney, Lloyd CL Hollenberg

2017-09-06

Magnetic resonance spectroscopy is one of the most important tools in chemical and bio-medical research. However, sensitivity limi..

Magneto-optical imaging of thin magnetic films using spins in diamond

David A Simpson, Jean-Philippe Tetienne, Julia M McCoey, Kumaravelu Ganesan, Liam T Hall, Steven Petrou, Robert E Scholten, Lloyd CL Hollenberg

2016-03-14

Imaging the fields of magnetic materials provides crucial insight into the physical and chemical processes surrounding magnetism, ..

Cortical alterations in a model for absence epilepsy and febrile seizures: In vivo findings in mice carrying a human GABA(A)R gamma2 subunit mutation

Jens Witsch, Daniel Golkowski, Thomas TG Hahn, Steven Petrou, Hartwig Spors

2015-05-01

Childhood absence epilepsy (CAE) is one of the most common forms of epilepsy among children. The study of a large Australian famil..

Sodium Channel beta 1 Subunit Localizes to Axon Initial Segments of Excitatory and Inhibitory Neurons and Shows Regional Heterogeneity in Mouse Brain

Verena C Wimmer, Rosemary C Harty, Kay L Richards, A Marie Phillips, Haruko Miyazaki, Nobuyuki Nukina, Steven Petrou

2015-04-01

The β1 subunit of voltage-gated sodium channels, Nav β1, plays multiple roles in neurons spanning electrophysiological modulation ..

'Neonatal' Na(v)1.2 reduces neuronal excitability and affects seizure susceptibility and behaviour

Elena V Gazina, Bryan TW Leaw, Kay L Richards, Verena C Wimmer, Tae H Kim, Timothy D Aumann, Travis J Featherby, Leonid Churilov, Vicki E Hammond, Christopher A Reid, Steven Petrou

2015-03-01

Developmentally regulated alternative splicing produces 'neonatal' and 'adult' isoforms of four Na(+) channels in human brain, NaV..

A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy

Mikko Muona, Samuel F Berkovic, Leanne M Dibbens, Karen L Oliver, Snezana Maljevic, Marta A Bayly, Tarja Joensuu, Laura Canafoglia, Silvana Franceschetti, Roberto Michelucci, Salla Markkinen, Sarah E Heron, Michael S Hildebrand, Eva Andermann, Frederick Andermann, Antonio Gambardella, Paolo Tinuper, Laura Licchetta, Ingrid E Scheffer, Chiara Criscuolo

2015-01-01

Progressive myoclonus epilepsies (PMEs) are a group of rare, inherited disorders manifesting with action myoclonus, tonic-clonic s..

Oxcarbazepine and its active metabolite, (S)-licarbazepine, exacerbate seizures in a mouse model of genetic generalized epilepsy

Tae Hwan Kim, Christopher A Reid, Steven Petrou

2015-01-01

Oxcarbazepine (OXC), widely used to treat focal epilepsy, is reported to exacerbate seizures in patients with generalized epilepsy..

Mapping somatosensory connectivity in adult mice using diffusion MRI tractography and super-resolution track density imaging

Kay Richards, Fernando Calamante, Jacques-Donald Tournier, Nyoman D Kurniawan, Farnoosh Sadeghian, Alexander R Retchford, Gabriel Davis Jones, Christopher A Reid, David C Reutens, Roger Ordidge, Alan Connelly, Steven Petrou

2014-11-15

In this study we combined ultra-high field diffusion MRI fiber tracking and super-resolution track density imaging (TDI) to map th..

Physiological and genetic analysis of multiple sodium channel variants in a model of genetic absence epilepsy

MK Oliva, TC McGarr, BJ Beyer, E Gazina, DI Kaplan, L Cordeiro, E Thomas, SD Dib-Hajj, SG Waxman, WN Frankel, S Petrou

2014-07-01

In excitatory neurons, SCN2A (NaV1.2) and SCN8A (NaV1.6) sodium channels are enriched at the axon initial segment. NaV1.6 is impli..

Reduced dendritic arborization and hyperexcitability of pyramidal neurons in a Scn1b-based model of Dravet syndrome

Christopher A Reid, Bryan Leaw, Kay L Richards, Robert Richardson, Verena Wimmer, Christiaan Yu, Elisa L Hill-Yardin, Holger Lerche, Ingrid E Scheffer, Samuel F Berkovic, Steven Petrou

2014-06-01

Epileptic encephalopathies, including Dravet syndrome, are severe treatment-resistant epilepsies with developmental regression. We..

Enhanced in vitro CA1 network activity in a sodium channel beta 1(C121W) subunit model of genetic epilepsy

Robert J Hatch, Christopher A Reid, Steven Petrou

2014-04-01

OBJECTIVE: A NaV β1(C121W) mouse model of human genetic epilepsy has enhanced neuronal excitability and temperature sensitivity at..

KCNT1 Gain of Function in 2 Epilepsy Phenotypes is Reversed by Quinidine

Carol J Milligan, Melody Li, Elena V Gazina, Sarah E Heron, Umesh Nair, Chantel Trager, Christopher A Reid, Anu Venkat, Donald P Younkin, Dennis J Dlugos, Slave Petrovski, David B Goldstein, Leanne M Dibbens, Ingrid E Scheffer, Samuel F Berkovic, Steven Petrou

2014-04-01

OBJECTIVE: Mutations in KCNT1 have been implicated in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and epilepsy of ..

Spike-and-wave discharge mediated reduction in hippocampal HCN1 channel function associates with learning deficits in a genetic mouse model of epilepsy

A Marie Phillips, Taehwan Kim, Ernesto Vargas, Steven Petrou, Christopher A Reid

2014-04-01

The GABAAγ2(R43Q) mouse is an established model of absence epilepsy displaying spontaneous spike-and-wave discharges (SWD) and ass..

Axon initial segment structural plasticity in animal models of genetic and acquired epilepsy

Rosemary C Harty, Tae Hwan Kim, Evan A Thomas, Lisa Cardamone, Nigel C Jones, Steven Petrou, Verena C Wimmer

2013-08-01

A novel form of neuronal plasticity, occurring at the axon initial segment (AIS), has recently been described. Lengthening of the ..

Network-specific mechanisms may explain the paradoxical effects of carbamazepine and phenytoin

Evan A Thomas, Steven Petrou

2013-07-01

PURPOSE: A common notion of the mechanism by which the antiepileptic drugs (AEDs) carbamazepine and phenytoin act is that they blo..

Hippocampal volume and cell density changes in a mouse model of human genetic epilepsy

Kay L Richards, Nyoman D Kurniawan, Zhengyi Yang, Tae Hwan Kim, Marianne D Keller, Jun Low, Jeremy FP Ullmann, Stacey Cole, Samuel Foong, Graham J Galloway, Christopher A Reid, George Paxinos, David C Reutens, Steven Petrou

2013-03-01

OBJECTIVE: The human γ-aminobutyric acid type A (GABAA)γ2R43Q (R43Q) mutation is associated with genetic epilepsy with febrile sei..

Multiple molecular mechanisms for a single GABA(A) mutation in epilepsy

Christopher A Reid, Taehwan Kim, A Marie Phillips, Jun Low, Samuel F Berkovic, Bernhard Luscher, Steven Petrou

2013-03-01

OBJECTIVE: To understand the molecular basis and differential penetrance of febrile seizures and absence seizures in patients with..

Multiple molecular mechanisms for a single GABAA mutation in epilepsy

CA Reid, T Kim, AM Phillips, J LOW, SF Berkovic, B Luscher, S Petrou

2013-01-01

Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy

Sarah E Heron, Katherine R Smith, Melanie Bahlo, Lino Nobili, Esther Kahana, Laura Licchetta, Karen L Oliver, Aziz Mazarib, Zaid Afawi, Amos Korczyn, Giuseppe Plazzi, Steven Petrou, Samuel F Berkovic, Ingrid E Scheffer, Leanne M Dibbens

2012-11-01

We performed genomic mapping of a family with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and intellectual and psy..

Sodium channels and the neurobiology of epilepsy

Megan Oliva, Samuel F Berkovic, Steven Petrou

2012-11-01

Voltage-gated sodium channels (VGSCs) are integral membrane proteins. They are essential for normal neurologic function and are, c..