GENETICS OF EPILEPSY
Grant number: 1006110 | Funding period: 2011 - 2015
Professor Scheffer and her collaborators lead the world in the discovery of the genetic causes of epilepsy. She will continue to identify new and refine known epilepsy syndromes and develop the classification of the epilepsies. Together with molecular colleagues, she will continue to discover the underlying genes causing this debilitating disorder leading to novel insights into the neurobiology. Her work may lead to new treatments and improve outcomes for people for epilepsy.
Related publications (41)
Genome-wide association study of febrile seizures identifies seven new loci implicating fever response and neuronal excitability genes
Line Skotte, João Fadista, Jonas Bybjerg-Grauholm, Vivek Appadurai, Michael S Hildebrand, Thomas F Hansen, Karina Banasik, Jakob Grove, Clara A Climent, Frank Geller, Carmen F Bjurström, Bjarni J Vilhjálmsson, Matthew Coleman, John A Damiano, Rosemary Burgess, Ingrid E Scheffer, Ole Birger Vesterager Pedersen, Christian Erikstrup, David Westergaard, Kaspar René Nielsen
<jats:title>ABSTRACT</jats:title><jats:p>Febrile seizures represent the most common type of pathological brain activity in young c..
Cerebrospinal fluid liquid biopsy for detecting somatic mosaicism in brain
Zimeng Ye, Zac Chatterton, Jahnvi Pflueger, John A Damiano, Lara McQuillan, Anthony Simon Harvey, Stephen Malone, Hongdo Do, Wirginia Maixner, Amy Schneider, Bernadette Nolan, Martin Wood, Wei Shern Lee, Greta Gillies, Kate Pope, Michael Wilson, Paul J Lockhart, Alexander Dobrovic, Ingrid E Scheffer, Melanie Bahlo
Brain somatic mutations are an increasingly recognized cause of epilepsy, brain malformations and autism spectrum disorders and ma..
Germline and Mosaic Variants in PRKACA and PRKACB Cause a Multiple Congenital Malformation Syndrome
Adrian Palencia-Campos, Phillip C Aoto, Erik MF Machal, Ana Rivera-Barahona, Patricia Soto-Bielicka, Daniela Bertinetti, Blaine Baker, Lily Vu, Francesca Piceci-Sparascio, Isabella Torrente, Eveline Boudin, Silke Peeters, Wim Van Hul, Celine Huber, Dominique Bonneau, Michael S Hildebrand, Matthew Coleman, Melanie Bahlo, Mark F Bennett, Amy L Schneider
PRKACA and PRKACB code for two catalytic subunits (Cα and Cβ) of cAMP-dependent protein kinase (PKA), a pleiotropic holoenzyme tha..
Pathogenic Variants in CEP85L Cause Sporadic and Familial Posterior Predominant Lissencephaly
Meng-Han Tsai, Alison M Muir, Won-Jing Wang, Yi-Ning Kang, Kun-Chuan Yang, Nian-Hsin Chao, Mei-Feng Wu, Ying-Chao Chang, Brenda E Porter, Laura A Jansen, Guillaume Sebire, Nicolas Deconinck, Wen-Lang Fan, Shih-Chi Su, Wen-Hung Chung, Edith P Almanza Fuerte, Michele G Mehaffey, Ching-Ching Ng, Chung-Kin Chan, Kheng-Seang Lim
Lissencephaly (LIS), denoting a "smooth brain," is characterized by the absence of normal cerebral convolutions with abnormalities..
SCN1A Variants in vaccine-related febrile seizures: A prospective study
John A Damiano, Lucy Deng, Wenhui Li, Rosemary Burgess, Amy L Schneider, Nigel W Crawford, Jim Buttery, Michael Gold, Peter Richmond, Kristine K Macartney, Michael S Hildebrand, Ingrid E Scheffer, Nicholas Wood, Samuel F Berkovic
OBJECTIVE: Febrile seizures may follow vaccination. Common variants in the sodium channel gene, SCN1A, are associated with febrile..
The Genetic Landscape of Epilepsy of Infancy with Migrating Focal Seizures
Rosemary Burgess, Shuyu Wang, Amy McTague, Katja E Boysen, Xiaoling Yang, Qi Zeng, Kenneth A Myers, Anne Rochtus, Marina Trivisano, Deepak Gill, Lynette G Sadleir, Nicola Specchio, Renzo Guerrini, Carla Marini, Yue-Hua Zhang, Heather C Mefford, Manju A Kurian, Annapurna H Poduri, Ingrid E Scheffer
OBJECTIVE: Epilepsy of infancy with migrating focal seizures (EIMFS) is one of the most severe developmental and epileptic encepha..
Inhibition of Upf2-Dependent Nonsense-Mediated Decay Leads to Behavioral and Neurophysiological Abnormalities by Activating the Immune Response
Jennifer L Johnson, Loredana Stoica, Yuwei Liu, Ping Jun Zhu, Abhisek Bhattacharya, Shelly A Buffington, Redwan Huq, N Tony Eissa, Ola Larsson, Bo T Porse, Deepti Domingo, Urwah Nawaz, Renee Carroll, Lachlan Jolly, Tom S Scerri, Hyung-Goo Kim, Amanda Brignell, Matthew J Coleman, Ruth Braden, Usha Kini
In humans, disruption of nonsense-mediated decay (NMD) has been associated with neurodevelopmental disorders (NDDs) such as autism..
Speech and language in bilateral perisylvian polymicrogyria: a systematic review
Ruth O Braden, Richard J Leventer, Anna Jansen, Ingrid E Scheffer, Angela T Morgan
AIM: We aimed to systematically review the speech production, language, and oral function phenotype of bilateral perisylvian polym..
A set of regulatory genes co-expressed in embryonic human brain is implicated in disrupted speech development
Else Eising, Amaia Carrion-Castillo, Arianna Vino, Edythe A Strand, Kathy J Jakielski, Thomas S Scerri, Michael S Hildebrand, Richard Webster, Alan Ma, Bernard Mazoyer, Clyde Francks, Melanie Bahlo, Ingrid E Scheffer, Angela T Morgan, Lawrence D Shriberg, Simon E Fisher
Genetic investigations of people with impaired development of spoken language provide windows into key aspects of human biology. O..
The epileptology of Koolen-de Vries syndrome: Electro-clinico-radiologic findings in 31 patients
Kenneth A Myers, Simone A Mandelstam, Georgia Ramantani, Elisabeth J Rushing, Bert B de Vries, David A Koolen, Ingrid E Scheffer
OBJECTIVE: This study was designed to describe the spectrum of epilepsy phenotypes in Koolen-de Vries syndrome (KdVS), a genetic s..
Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases
Holly AF Stessman, Bo Xiong, Bradley P Coe, Tianyun Wang, Kendra Hoekzema, Michaela Fenckova, Malin Kvarnung, Jennifer Gerdts, Sandy Trinh, Nele Cosemans, Laura Vives, Janice Lin, Tychele N Turner, Gijs Santen, Claudia Ruivenkamp, Marjolein Kriek, Arie van Haeringen, Emmelien Aten, Kathryn Friend, Jan Liebelt
Gene-disruptive mutations contribute to the biology of neurodevelopmental disorders (NDDs), but most of the related pathogenic gen..
Frequency of CNKSR2 mutation in the X-linked epilepsy-aphasia spectrum
John A Damiano, Rosemary Burgess, Sara Kivity, Tally Lerman-Sagie, Zaid Afawi, Ingrid E Scheffer, Samuel F Berkovic, Michael S Hildebrand
Synaptic proteins are critical to neuronal function in the brain, and their deficiency can lead to seizures and cognitive impairme..
De novo SCN1A pathogenic variants in the GEFS plus spectrum: Not always a familial syndrome
Kenneth A Myers, Rosemary Burgess, Zaid Afawi, John A Damiano, Samuel F Berkovic, Michael S Hildebrand, Ingrid E Scheffer
Genetic epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome characterized by heterogeneous phenotypes rang..
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..
Is FGF13 a major contributor to genetic epilepsy with febrile seizures plus?
Kristin A Rigbye, Peter M van Hasselt, Rosemary Burgess, John A Damiano, Saul A Mullen, Slave Petrovski, Ram S Puranam, Koen LI van Gassen, Jozef Gecz, Ingrid E Scheffer, James O McNamara, Samuel F Berkovic, Michael S Hildebrand
Mutation of fibroblast growth factor 13 (FGF13) has recently been implicated in genetic epilepsy with febrile seizures plus (GEFS+..
Mutations of the Sonic Hedgehog Pathway Underlie Hypothalamic Hamartoma with Gelastic Epilepsy
Michael S Hildebrand, Nicole G Griffin, John A Damiano, Elisa J Cops, Rosemary Burgess, Ezgi Ozturk, Nigel C Jones, Richard J Leventer, Jeremy L Freeman, A Simon Harvey, Lynette G Sadleir, Ingrid E Scheffer, Heather Major, Benjamin W Darbro, Andrew S Allen, David B Goldstein, John F Kerrigan, Samuel F Berkovic, Erin L Heinzen
Hypothalamic hamartoma (HH) with gelastic epilepsy is a well-recognized drug-resistant epilepsy syndrome of early life.(1) Surgica..
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..
A mutation in COL4A2 causes autosomal dominant porencephaly with cataracts
Thuong T Ha, Lynette G Sadleir, Simone A Mandelstam, Sarah J Paterson, Ingrid E Scheffer, Jozef Gecz, Mark A Corbett
Mutations in COL4A1 are well described and result in brain abnormalities manifesting with severe neurological deficits including c..
Exome-based analysis of cardiac arrhythmia, respiratory control, and epilepsy genes in sudden unexpected death in epilepsy
Richard D Bagnall, Douglas E Crompton, Slave Petrovski, Lien Lam, Carina Cutmore, Sarah I Garry, Lynette G Sadleir, Leanne M Dibbens, Anita Cairns, Sara Kivity, Zaid Afawi, Brigid M Regan, Johan Duflou, Samuel F Berkovic, Ingrid E Scheffer, Christopher Semsarian
OBJECTIVE: The leading cause of epilepsy-related premature mortality is sudden unexpected death in epilepsy (SUDEP). The cause of ..
Mutations in the Mammalian Target of Rapamycin Pathway Regulators NPRL2 and NPRL3 Cause Focal Epilepsy
Michael G Ricos, Bree L Hodgson, Tommaso Pippucci, Akzam Saidin, Yeh Sze Ong, Sarah E Heron, Laura Licchetta, Francesca Bisulli, Marta A Bayly, James Hughes, Sara Baldassari, Flavia Palombo, Margherita Santucci, Stefano Meletti, Samuel F Berkovic, Guido Rubboli, Paul Q Thomas, Ingrid E Scheffer, Paolo Tinuper, Joel Geoghegan
OBJECTIVE: Focal epilepsies are the most common form observed and have not generally been considered to be genetic in origin. Rece..
Loss of synaptic Zn2 transporter function increases risk of febrile seizures
Michael S Hildebrand, A Marie Phillips, Saul A Mullen, Paul A Adlard, Katia Hardies, John A Damiano, Verena Wimmer, Susannah T Bellows, Jacinta M McMahon, Rosemary Burgess, Rik Hendrickx, Sarah Weckhuysen, Arvid Suls, Peter De Jonghe, Ingrid E Scheffer, Steven Petrou, Samuel F Berkovic, Christopher A Reid
Febrile seizures (FS) are the most common seizure syndrome and are potentially a prelude to more severe epilepsy. Although zinc (Z..
Evaluation of multiple putative risk alleles within the 15q13.3 region for genetic generalized epilepsy
John A Damiano, Saul A Mullen, Michael S Hildebrand, Susannah T Bellows, Kate M Lawrence, Todor Arsov, Leanne Dibbens, Heather Major, Hans-Henrik M Dahl, Heather C Mefford, Benjamin W Darbro, Ingrid E Scheffer, Samuel F Berkovic
The chromosome 15q13.3 region has been implicated in epilepsy, intellectual disability and neuropsychiatric disorders, especially ..
Mutation of the nuclear lamin gene LMNB2 in progressive myoclonus epilepsy with early ataxia
John A Damiano, Zaid Afawi, Melanie Bahlo, Monika Mauermann, Adel Misk, Todor Arsov, Karen L Oliver, Hans-Henrik M Dahl, A Eliot Shearer, Richard JH Smith, Nathan E Hall, Khalid Mahmood, Richard J Leventer, Ingrid E Scheffer, Mikko Muona, Anna-Elina Lehesjoki, Amos D Korczyn, Harald Herrmann, Samuel F Berkovic, Michael S Hildebrand
We studied a consanguineous Palestinian Arab family segregating an autosomal recessive progressive myoclonus epilepsy (PME) with e..
PRIMA1 mutation: a new cause of nocturnal frontal lobe epilepsy
Michael S Hildebrand, Rick Tankard, Elena V Gazina, John A Damiano, Kate M Lawrence, Hans-Henrik M Dahl, Brigid M Regan, Aiden Eliot Shearer, Richard JH Smith, Carla Marini, Renzo Guerrini, Angelo Labate, Antonio Gambardella, Paolo Tinuper, Laura Lichetta, Sara Baldassari, Francesca Bisulli, Tommaso Pippucci, Ingrid E Scheffer, Christopher A Reid
OBJECTIVE: Nocturnal frontal lobe epilepsy (NFLE) can be sporadic or autosomal dominant; some families have nicotinic acetylcholin..
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..
"It's good to know": Experiences of gene identification and result disclosure in familial epilepsies
Danya F Vears, Karen L Dunn, Samantha A Wake, Ingrid E Scheffer
Recognition of the role of genetics in the epilepsies has increased dramatically, impacting on clinical practice across many epile..
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..
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..
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..
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..
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..
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 ..
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..
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..
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..
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 Mutations Cause Benign Familial Infantile Epilepsy and Infantile Convulsions with Choreoathetosis Syndrome
Sarah E Heron, Bronwyn E Grinton, Sara Kivity, Zaid Afawi, Sameer M Zuberi, James N Hughes, Clair Pridmore, Bree L Hodgson, Xenia Iona, Lynette G Sadleir, James Pelekanos, Eric Herlenius, Hadassa Goldberg-Stern, Haim Bassan, Eric Haan, Amos D Korczyn, Alison E Gardner, Mark A Corbett, Jozef Gecz, Paul Q Thomas
Benign familial infantile epilepsy (BFIE) is a self-limited seizure disorder that occurs in infancy and has autosomal-dominant inh..