Epilepsy: Molecular basis and mechanisms in the era of functional genomics
Grant number: 400121
The team comprises of neurologists with a special interest in epilepsy (both adult and child) molecular geneticists, physiologists and brain imaging specialists. The team leads the world in the discovery of the genetic causes of epilepsy and epilepsy associated with intellectual disability. The team will continue to identify the genes underlying epilepsy, and study how genetic variations result in the development of seizures and will continue to develop advanced imaging techniques for these studies. This will include extensive laboratory studies, including the development of mice with the exact mutations that we find in the human condition. Stateof-the-art imaging techniques with magnetic re..View full description
Related publications (20)
Two distinct symptom-based phenotypes of depression in epilepsy yield specific clinical and etiological insights
Genevieve Rayner, Graeme D Jackson, Sarah J Wilson
Depression is common but underdiagnosed in epilepsy. A quarter of patients meet criteria for a depressive disorder, yet few receiv..
A novel X-linked trichothiodystrophy associated with a nonsense mutation in RNF113A
Mark A Corbett, Tracy Dudding-Byth, Patricia A Crock, Elena Botta, Louise M Christie, Tiziana Nardo, Giuseppina Caligiuri, Lynne Hobson, Jackie Boyle, Albert Mansour, Kathryn L Friend, Jo Crawford, Graeme Jackson, Lucianne Vandeleur, Anna Hackett, Patrick Tarpey, Michael R Stratton, Gillian Turner, Jozef Gecz, Michael Field
BACKGROUND: Trichothiodystrophy (TTD) is a group of rare autosomal recessive disorders that variably affect a wide range of organs..
Genetics of epilepsy The testimony of twins in the molecular era
Lata Vadlamudi, Roger L Milne, Kate Lawrence, Sarah E Heron, Jazmin Eckhaus, Deborah Keay, Mary Connellan, Yvonne Torn-Broers, R Anne Howell, John C Mulley, Ingrid E Scheffer, Leanne M Dibbens, John L Hopper, Samuel F Berkovic
OBJECTIVE: Analysis of twins with epilepsy to explore the genetic architecture of specific epilepsies, to evaluate the applicabili..
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
In excitatory neurons, SCN2A (NaV1.2) and SCN8A (NaV1.6) sodium channels are enriched at the axon initial segment. NaV1.6 is impli..
Elemental Spatial and Temporal Association Formation in Left Temporal Lobe Epilepsy
Christopher FA Benjamin, Michael M Saling, Amanda G Wood, David C Reutens
The mesial temporal lobe (MTL) is typically understood as a memory structure in clinical settings, with the sine qua non of MTL da..
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
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
OBJECTIVE: A NaV β1(C121W) mouse model of human genetic epilepsy has enhanced neuronal excitability and temperature sensitivity at..
Low glycaemic index diet reduces seizure susceptibility in a syndrome-specific mouse model of generalized epilepsy
Tae Hwan Kim, Steven Petrou, Christopher A Reid
PURPOSE: Clinical evidence suggests that low glycaemic index diets are effective at reducing seizure frequency potentially through..
Copy number variants are frequent in genetic generalized epilepsy with intellectual disability
Saul A Mullen, Gemma L Carvill, Susannah Bellows, Marta A Bayly, Samuel F Berkovic, Leanne M Dibbens, Ingrid E Scheffer, Heather C Mefford
OBJECTIVE: We examined whether copy number variants (CNVs) were more common in those with a combination of intellectual disability..
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
A novel form of neuronal plasticity, occurring at the axon initial segment (AIS), has recently been described. Lengthening of the ..
Perturbations in cortical development and neuronal network excitability arising from prenatal exposure to benzodiazepines in mice
Matilda Haas, Zhengdong Qu, Tae Hwan Kim, Ernesto Vargas, Kenneth Campbell, Steven Petrou, Seong-Seng Tan, Christopher A Reid, Julian Heng
During brain development, many factors influence the assembly and final positioning of cortical neurons, and this process is essen..
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
OBJECTIVE: To understand the molecular basis and differential penetrance of febrile seizures and absence seizures in patients with..
Two lines of transgenic mice expressing cre-recombinase exhibit increased seizure susceptibility
Tae Hwan Kim, Kay Richards, Julian Heng, Steven Petrou, Christopher A Reid
Conditional mouse models based on the Cre-recombinase (Cre)-loxP method are a powerful tool for determining the spatial and tempor..
Genetic and pharmacological modulation of giant depolarizing potentials in the neonatal hippocampus associates with increased seizure susceptibility
Ernesto Vargas, Steven Petrou, Christopher A Reid
The expression of Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) is responsible for high intracellular Cl(-) resulting in the excitatory ..
Triheptanoin reduces seizure susceptibility in a syndrome-specific mouse model of generalized epilepsy
Tae Hwan Kim, Karin Borges, Steven Petrou, Christopher A Reid
Triheptanoin is a triglyceride containing heptanoate, an odd-chained medium fatty acid that is metabolized to produce propionyl-Co..
Benign Neonatal Sleep Myoclonus: An Autosomal Dominant Form Not Allelic to KCNQ2 or KCNQ3
Zaid Afawi, Haim Bassan, Sarah Heron, Karen Oliver, Rachel Straussberg, Ingrid Scheffer, Richard Leventer, Amos Korczyn, Samuel Berkovic
Benign neonatal sleep myoclonus is an uncommon, nonepileptic disorder characterized by myoclonic jerks appearing in the neonatal p..