EPILEPSY: A 'PATIENT TO BENCH AND BACK TO PATIENT' PROGRAM ABOUT UNDERSTANDING THE CAUSES OF SEIZURE DISORDERS.
Grant number: 628952 | Funding period: 2011 - 2015
The team is comprised of neurologists, molecular geneticists, physiologists and brain imaging specialists and leads the world in the discovery of the genetic causes of epilepsy. They will continue to identify genes underlying epilepsy and study how genetic variations result in development of seizures. Advanced brain imaging will be used to understand the effects of genetic variation on brain structure and function. This study may lead to new diagnostic methods and treatments for epilepsy.
Related publications (45)
Evaluation of non-coding variation in GLUT1 deficiency
Yu-Chi Liu, Jia Wei Audrey Lee, Susannah T Bellows, John A Damiano, Saul A Mullen, Samuel F Berkovic, Melanie Bahlo, Ingrid E Scheffer, Michael S Hildebrand
AIM: Loss-of-function mutations in SLC2A1, encoding glucose transporter-1 (GLUT-1), lead to dysfunction of glucose transport acros..
Dominant KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy
Mark A Corbett, Susannah T Bellows, Melody Li, Renee Carroll, Silvana Micallef, Gemma L Carvill, Candace T Myers, Katherine B Howell, Snezana Maljevic, Holger Lerche, Elena V Gazina, Heather C Mefford, Melanie Bahlo, Samuel F Berkovic, Steven Petrou, Ingrid E Scheffer, Jozef Gecz
OBJECTIVE: To identify the genetic basis of a family segregating episodic ataxia, infantile seizures, and heterogeneous epilepsies..
Hippocampal malrotation is an anatomic variant and has no clinical significance in MRI-negative temporal lobe epilepsy
Meng-Han Tsai, David N Vaughan, Yuliya Perchyonok, Greg J Fitt, Ingrid E Scheffer, Samuel F Berkovic, Graeme D Jackson
OBJECTIVE: There is considerable difficulty in diagnosing hippocampal malrotation (HIMAL), with different criteria of variable rel..
Diagnosis and misdiagnosis of adult neuronal ceroid lipofuscinosis (Kufs disease)
Samuel F Berkovic, John F Staropoli, Stirling Carpenter, Karen L Oliver, Stanislav Kmoch, Glenn W Anderson, John A Damiano, Michael S Hildebrand, Katherine B Sims, Susan L Cotman, Melanie Bahlo, Katherine R Smith, Maxime Cadieux-Dion, Patrick Cossette, Ivana Jedlickova, Anna Pristoupilova, Sara E Mole
OBJECTIVE: To critically re-evaluate cases diagnosed as adult neuronal ceroid lipofuscinosis (ANCL) in order to aid clinicopatholo..
TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features
Simona Balestrini, Mathieu Milh, Claudia Castiglioni, Kevin Luethy, Mattea J Finelli, Patrik Verstreken, Aaron Cardon, Barbara Gnidovec Strazisar, J Lloyd Holder, Gaetan Lesca, Maria M Mancardi, Anne L Poulat, Gabriela M Repetto, Siddharth Banka, Leonilda Bilo, Laura E Birkeland, Friedrich Bosch, Knut Brockmann, J Helen Cross, Diane Doummar
OBJECTIVE: To evaluate the phenotypic spectrum associated with mutations in TBC1D24. METHODS: We acquired new clinical, EEG, and n..
A targeted resequencing gene panel for focal epilepsy
Michael S Hildebrand, Candace T Myers, Gemma L Carvill, Brigid M Regan, John A Damiano, Saul A Mullen, Mark R Newton, Umesh Nair, Elena V Gazina, Carol J Milligan, Christopher A Reid, Steven Petrou, Ingrid E Scheffer, Samuel F Berkovic, Heather C Mefford
OBJECTIVES: We report development of a targeted resequencing gene panel for focal epilepsy, the most prevalent phenotypic group of..
Multiplex families with epilepsy Success of clinical and molecular genetic characterization
Zaid Afawi, Karen L Oliver, Sara Kivity, Aziz Mazarib, Ilan Blatt, Miriam Y Neufeld, Katherine L Helbig, Hadassa Goldberg-Stern, Adel J Misk, Rachel Straussberg, Simri Walid, Muhammad Mahajnah, Tally Lerman-Sagie, Bruria Ben-Zeev, Esther Kahana, Rafik Masalha, Uri Kramer, Dana Ekstein, Zamir Shorer, Robyn H Wallace
OBJECTIVE: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim ..
Brain regions with abnormal network properties in severe epilepsy of Lennox-Gastaut phenotype: Multivariate analysis of task-free fMRI
Mangor Pedersen, Evan K Curwood, John S Archer, David F Abbott, Graeme D Jackson
OBJECTIVE: Lennox-Gastaut syndrome, and the similar but less tightly defined Lennox-Gastaut phenotype, describe patients with seve..
Mutations in KCNT1 cause a spectrum of focal epilepsies
Rikke S Moller, Sarah E Heron, Line HG Larsen, Chiao Xin Lim, Michael G Ricos, Marta A Bayly, Marjan JA van Kempen, Sylvia Klinkenberg, Ian Andrews, Kent Kelley, Gabriel M Ronen, David Callen, Jacinta M McMahon, Simone C Yendle, Gemma L Carvill, Heather C Mefford, Rima Nabbout, Annapurna Poduri, Pasquale Striano, Maria G Baglietto
Autosomal dominant mutations in the sodium-gated potassium channel subunit gene KCNT1 have been associated with two distinct seizu..
Familial neonatal seizures in 36 families: Clinical and genetic features correlate with outcome
Bronwyn E Grinton, Sarah E Heron, James T Pelekanos, Sameer M Zuberi, Sara Kivity, Zaid Afawi, Tristiana C Williams, Dan M Casalaz, Simone Yendle, Ilan Linder, Dorit Lev, Tally Lerman-Sagie, Stephen Malone, Haim Bassan, Hadassa Goldberg-Stern, Thorsten Stanley, Michael Hayman, Sophie Calvert, Amos D Korczyn, Michael Shevell
OBJECTIVE: We evaluated seizure outcome in a large cohort of familial neonatal seizures (FNS), and examined phenotypic overlap wit..
Seizures Are Regulated by Ubiquitin-specific Peptidase 9 X-linked (USP9X), a De-Ubiquitinase
Lily Paemka, Vinit B Mahajan, Salleh N Ehaideb, Jessica M Skeie, Men Chee Tan, Shu Wu, Allison J Cox, Levi P Sowers, Jozef Gecz, Lachlan Jolly, Polly J Ferguson, Benjamin Darbro, Amy Schneider, Ingrid E Scheffer, Gemma L Carvill, Heather C Mefford, Hatem El-Shanti, Stephen A Wood, J Robert Manak, Alexander G Bassuk
Epilepsy is a common disabling disease with complex, multifactorial genetic and environmental etiology. The small fraction of epil..
GRIN2A An aptly named gene for speech dysfunction
Samantha J Turner, Angela K Mayes, Andrea Verhoeven, Simone A Mandelstam, Angela T Morgan, Ingrid E Scheffer
OBJECTIVE: To delineate the specific speech deficits in individuals with epilepsy-aphasia syndromes associated with mutations in t..
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
Progressive myoclonus epilepsies (PMEs) are a group of rare, inherited disorders manifesting with action myoclonus, tonic-clonic s..
16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy
Eva M Reinthaler, Dennis Lal, Sebastien Lebon, Michael S Hildebrand, Hans-Henrik M Dahl, Brigid M Regan, Martha Feucht, Hannelore Steinboeck, Birgit Neophytou, Gabriel M Ronen, Laurian Roche, Ursula Gruber-Sedlmayr, Julia Geldner, Edda Haberlandt, Per Hoffmann, Stefan Herms, Christian Gieger, Melanie Waldenberger, Andre Franke, Michael Wittig
Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a comple..
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
In this study we combined ultra-high field diffusion MRI fiber tracking and super-resolution track density imaging (TDI) to map th..
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..
Genetic analysis of PHOX2B in sudden unexpected death in epilepsy cases
Richard D Bagnall, Douglas E Crompton, Carina Cutmore, Brigid M Regan, Samuel F Berkovic, Ingrid E Scheffer, Christopher Semsarian
OBJECTIVE: To determine the contribution of sequence variations in PHOX2B to sudden unexpected death in epilepsy (SUDEP). METHODS:..
Harnessing Gene Expression Networks to Prioritize Candidate Epileptic Encephalopathy Genes
Karen L Oliver, Vesna Lukic, Natalie P Thorne, Samuel F Berkovic, Ingrid E Scheffer, Melanie Bahlo
We apply a novel gene expression network analysis to a cohort of 182 recently reported candidate Epileptic Encephalopathy genes to..
A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation
Martin Puskarjov, Patricia Seja, Sarah E Heron, Tristiana C Williams, Faraz Ahmad, Xenia Iona, Karen L Oliver, Bronwyn E Grinton, Laszlo Vutskits, Ingrid E Scheffer, Steven Petrou, Peter Blaesse, Leanne M Dibbens, Samuel F Berkovic, Kai Kaila
Genetic variation in SLC12A5 which encodes KCC2, the neuron-specific cation-chloride cotransporter that is essential for hyperpola..
Mutations in Mammalian Target of Rapamycin Regulator DEPDC5 Cause Focal Epilepsy with Brain Malformations
Ingrid E Scheffer, Sarah E Heron, Brigid M Regan, Simone Mandelstam, Douglas E Crompton, Bree L Hodgson, Laura Licchetta, Federica Provini, Francesca Bisulli, Lata Vadlamudi, Jozef Gecz, Alan Connelly, Paolo Tinuper, Michael G Ricos, Samuel F Berkovic, Leanne M Dibbens
We recently identified DEPDC5 as the gene for familial focal epilepsy with variable foci and found mutations in >10% of small fami..
Reading difficulty is associated with failure to lateralize temporooccipital function
Chris Tailby, David L Weintrob, Michael M Saling, Carly Fitzgerald, Graeme D Jackson
OBJECTIVE: Studies of focal epilepsy have revealed abnormalities of language organization; however, little attention has been paid..
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
OBJECTIVE: Mutations in KCNT1 have been implicated in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and epilepsy of ..
Glucose metabolism transporters and epilepsy: Only GLUT1 has an established role
Michael S Hildebrand, John A Damiano, Saul A Mullen, Susannah T Bellows, Karen L Oliver, Hans-Henrik M Dahl, Ingrid E Scheffer, Samuel F Berkovic
The availability of glucose, and its glycolytic product lactate, for cerebral energy metabolism is regulated by specific brain tra..
Changes in singing performance and fMRI activation following right temporal lobe surgery
Sarah J Wilson, David F Abbott, Chris Tailby, Ellen C Gentle, Dawn L Merrett, Graeme D Jackson
INTRODUCTION: This study arose in the context of having to estimate risk to the musical abilities of a trained singer (patient A.M..
Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A
Dalia Kasperaviciute, Claudia B Catarino, Mar Matarin, Costin Leu, Jan Novy, Anna Tostevin, Barbara Leal, Ellen VS Hessel, Kerstin Hallmann, Michael S Hildebrand, Hans-Henrik M Dahl, Mina Ryten, Daniah Trabzuni, Adaikalavan Ramasamy, Saud Alhusaini, Colin P Doherty, Thomas Dorn, Joerg Hansen, Guenter Kraemer, Bernhard J Steinhoff
Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seiz..
GRIN2A mutations cause epilepsy-aphasia spectrum disorders
Gemma L Carvill, Brigid M Regan, Simone C Yendle, Brian J O'Roak, Natalia Lozovaya, Nadine Bruneau, Nail Burnashev, Adiba Khan, Joseph Cook, Eileen Geraghty, Lynette G Sadleir, Samantha J Turner, Meng-Han Tsai, Richard Webster, Robert Ouvrier, John A Damiano, Samuel F Berkovic, Jay Shendure, Michael S Hildebrand, Pierre Szepetowski
Epilepsy-aphasia syndromes (EAS) are a group of rare, severe epileptic encephalopathies of unknown etiology with a characteristic ..
Networks underlying paroxysmal fast activity and slow spike and wave in Lennox-Gastaut syndrome
Neelan Pillay, John S Archer, Radwa AB Badawy, Danny F Flanagan, Samuel F Berkovic, Graeme Jackson
OBJECTIVE: To use EEG-fMRI to determine which structures are critically involved in the generation of paroxysmal fast activity (PF..
An automated method for identifying artifact in independent component analysis of resting-state fMRI
Kaushik Bhaganagarapu, Graeme D Jackson, David F Abbott
An enduring issue with data-driven analysis and filtering methods is the interpretation of results. To assist, we present an autom..
Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1
Gemma L Carvill, Sinead B Heavin, Simone C Yendle, Jacinta M McMahon, Brian J O'Roak, Joseph Cook, Adiba Khan, Michael O Dorschner, Molly Weaver, Sophie Calvert, Stephen Malone, Geoffrey Wallace, Thorsten Stanley, Ann ME Bye, Andrew Bleasel, Katherine B Howell, Sara Kivity, Mark T Mackay, Victoria Rodriguez-Casero, Richard Webster
Epileptic encephalopathies are a devastating group of epilepsies with poor prognosis, of which the majority are of unknown etiolog..
Absence epilepsy subnetworks revealed by event-related independent components analysis of functional magnetic resonance imaging
Richard AJ Masterton, Patrick W Carney, David F Abbott, Graeme D Jackson
PURPOSE: The aim of this study was to provide better spatiotemporal description of the brain activity observed during generalized ..
Mutations in DEPDC5 cause familial focal epilepsy with variable foci
Leanne M Dibbens, Boukje de Vries, Simona Donatello, Sarah E Heron, Bree L Hodgson, Satyan Chintawar, Douglas E Crompton, James N Hughes, Susannah T Bellows, Karl Martin Klein, Petra MC Callenbach, Mark A Corbett, Alison E Gardner, Sara Kivity, Xenia Iona, Brigid M Regan, Claudia M Weller, Denis Crimmins, Terence J O'Brien, Rosa Guerrero-Lopez
The majority of epilepsies are focal in origin, with seizures emanating from one brain region. Although focal epilepsies often ari..
Mutations in PRRT2 are not a common cause of infantile epileptic encephalopathies
Sarah E Heron, Yeh Sze Ong, Simone C Yendle, Jacinta M McMahon, Samuel F Berkovic, Ingrid E Scheffer, Leanne M Dibbens
Heterozygous mutations in PRRT2 have recently been identified as the major cause of autosomal dominant benign familial infantile e..
Recent advances in the molecular genetics of epilepsy
Michael S Hildebrand, Hans-Henrik M Dahl, John Anthony Damiano, Richard JH Smith, Ingrid E Scheffer, Samuel F Berkovic
Recent advances in molecular genetics have translated into the increasing utilisation of genetic testing in the routine clinical p..
Mapping brain activity using event-related independent components analysis (eICA): Specific advantages for EEG-fMRI
Richard AJ Masterton, Graeme D Jackson, David F Abbott
Event-related analyses of functional MRI (fMRI) typically assume that the onset and offset of neuronal activity match stimuli onse..
Cathepsin F mutations cause Type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis
Katherine R Smith, Hans-Henrik M Dahl, Laura Canafoglia, Eva Andermann, John Damiano, Michela Morbin, Amalia C Bruni, Giorgio Giaccone, Patrick Cossette, Paul Saftig, Joachim Groetzinger, Michael Schwake, Frederick Andermann, John F Staropoli, Katherine B Sims, Sara E Mole, Silvana Franceschetti, Noreen A Alexander, Jonathan D Cooper, Harold A Chapman
Kufs disease, an adult-onset neuronal ceroid lipofuscinosis, is challenging to diagnose and genetically heterogeneous. Mutations i..
'North Sea' progressive myoclonus epilepsy: phenotype of subjects with GOSR2 mutation
Lysa Boisse Lomax, Marta A Bayly, Helle Hjalgrim, Rikke S Moller, Annemarie M Vlaar, Kari M Aaberg, Iris Marquardt, Luke C Gandolfo, Michel Willemsen, Erik-Jan Kamsteeg, John D O'Sullivan, G Christoph Korenke, Bastiaan R Bloem, Irenaeus F de Coo, Judith MA Verhagen, Ines Said, Trine Prescott, Asbjorg Stray-Pedersen, Magnhild Rasmussen, Danya F Vears
We previously identified a homozygous mutation in the Golgi SNAP receptor complex 2 gene (GOSR2) in six patients with progressive ..
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
We performed genomic mapping of a family with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and intellectual and psy..
PRRT2 phenotypic spectrum includes sporadic and fever-related infantile seizures
Ingrid E Scheffer, Bronwyn E Grinton, Sarah E Heron, Sara Kivity, Zaid Afawi, Xenia Iona, Hadassa Goldberg-Stern, Maria Kinali, Ian Andrews, Renzo Guerrini, Carla Marini, Lynette G Sadleir, Samuel F Berkovic, Leanne M Dibbens
OBJECTIVE: Benign familial infantile epilepsy (BFIE) is an autosomal dominant epilepsy syndrome characterized by afebrile seizures..
Familial focal epilepsy with variable foci mapped to chromosome 22q12: Expansion of the phenotypic spectrum
Karl Martin Klein, Terence J O'Brien, Kavita Praveen, Sarah E Heron, John C Mulley, Simon Foote, Samuel F Berkovic, Ingrid E Scheffer
We aimed to refine the phenotypic spectrum and map the causative gene in two families with familial focal epilepsy with variable f..