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2. Exome sequencing of ATP1A3-negative cases of alternating hemiplegia of childhood reveals SCN2A as a novel causative gene

Author

Panagiotakaki, Eleni, Tiziano, Francesco D., Mikati, Mohamad A., Vijfhuizen, Lisanne S., Nicole, Sophie, Lesca, Gaetan, Abiusi, Emanuela, Novelli, Agnese, Di Pietro, Lorena, Harder, Aster V. E., Walley, Nicole M., De Grandis, Elisa, Poulat, Anne-Lise, Portes, Vincent Des, Lépine, Anne, Nassogne, Marie-Cecile, Arzimanoglou, Alexis, Vavassori, Rosaria, Koenderink, Jan, Thompson, Christopher H., George, Jr., Alfred L., Gurrieri, Fiorella, van den Maagdenberg, Arn M. J. M., and Heinzen, Erin L.

Published
2024
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3. Post-zygotic rescue of meiotic errors causes brain mosaicism and focal epilepsy

Author

Miller, Katherine E., Rivaldi, Adithe C., Shinagawa, Noriyuki, Sran, Sahib, Navarro, Jason B., Westfall, Jesse J., Miller, Anthony R., Roberts, Ryan D., Akkari, Yassmine, Supinger, Rachel, Hester, Mark E., Marhabaie, Mohammad, Gade, Meethila, Lu, Jinfeng, Rodziyevska, Olga, Bhattacharjee, Meenakshi B., Von Allmen, Gretchen K., Yang, Edward, Lidov, Hart G. W., Harini, Chellamani, Shah, Manish N., Leonard, Jeffrey, Pindrik, Jonathan, Shaikhouni, Ammar, Goldman, James E., Pierson, Christopher R., Thomas, Diana L., Boué, Daniel R., Ostendorf, Adam P., Mardis, Elaine R., Poduri, Annapurna, Koboldt, Daniel C., Heinzen, Erin L., and Bedrosian, Tracy A.

Published
2023
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5. Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations

Author

Stevelink, Remi, Luykx, Jurjen J, Lin, Bochao D, Leu, Costin, Lal, Dennis, Smith, Alexander W, Schijven, Dick, Carpay, Johannes A, Rademaker, Koen, Baldez, Roiza A Rodrigues, Devinsky, Orrin, Braun, Kees PJ, Jansen, Floor E, Smit, Dirk JA, Koeleman, Bobby PC, Abou‐Khalil, Bassel, Auce, Pauls, Avbersek, Andreja, Bahlo, Melanie, Balding, David J, Bast, Thomas, Baum, Larry, Becker, Albert J, Becker, Felicitas, Berghuis, Bianca, Berkovic, Samuel F, Boysen, Katja E, Bradfield, Jonathan P, Brody, Lawrence C, Buono, Russell J, Campbell, Ellen, Cascino, Gregory D, Catarino, Claudia B, Cavalleri, Gianpiero L, Cherny, Stacey S, Chinthapalli, Krishna, Coffey, Alison J, Compston, Alastair, Coppola, Antonietta, Cossette, Patrick, Craig, John J, de Haan, Gerrit‐Jan, De Jonghe, Peter, de Kovel, Carolien GF, Delanty, Norman, Depondt, Chantal, Dlugos, Dennis J, Doherty, Colin P, Elger, Christian E, Eriksson, Johan G, Ferraro, Thomas N, Feucht, Martha, Francis, Ben, Franke, Andre, French, Jacqueline A, Freytag, Saskia, Gaus, Verena, Geller, Eric B, Gieger, Christian, Glauser, Tracy, Glynn, Simon, Goldstein, David B, Gui, Hongsheng, Guo, Youling, Haas, Kevin F, Hakonarson, Hakon, Hallmann, Kerstin, Haut, Sheryl, Heinzen, Erin L, Helbig, Ingo, Hengsbach, Christian, Hjalgrim, Helle, Iacomino, Michele, Ingason, Andrés, Jamnadas‐Khoda, Jennifer, Johnson, Michael R, Kälviäinen, Reetta, Kantanen, Anne‐Mari, Kasperavičiūte, Dalia, Trenite, Dorothee Kasteleijn‐Nolst, Kirsch, Heidi E, Knowlton, Robert C, Krause, Roland, Krenn, Martin, Kunz, Wolfram S, Kuzniecky, Ruben, Kwan, Patrick, Lau, Yu‐Lung, Lehesjoki, Anna‐Elina, Lerche, Holger, Lieb, Wolfgang, Lindhout, Dick, Lo, Warren D, Lopes‐Cendes, Iscia, Lowenstein, Daniel H, Malovini, Alberto, Marson, Anthony G, Mayer, Thomas, McCormack, Mark, and Mills, James L

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Genetics, Brain Disorders, Clinical Research, Human Genome, Neurodegenerative, Epilepsy, 2.1 Biological and endogenous factors, Aetiology, Neurological, Adult, Algorithms, Beta Rhythm, Cohort Studies, Databases, Factual, Electroencephalography, Epilepsy, Generalized, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Mendelian Randomization Analysis, Risk Assessment, Theta Rhythm, beta power, EEG, generalized epilepsy, GGE, oscillations, PRS, International League Against Epilepsy Consortium on Complex Epilepsies, Epi25 Collaborative, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveParoxysmal epileptiform abnormalities on electroencephalography (EEG) are the hallmark of epilepsies, but it is uncertain to what extent epilepsy and background EEG oscillations share neurobiological underpinnings. Here, we aimed to assess the genetic correlation between epilepsy and background EEG oscillations.MethodsConfounding factors, including the heterogeneous etiology of epilepsies and medication effects, hamper studies on background brain activity in people with epilepsy. To overcome this limitation, we compared genetic data from a genome-wide association study (GWAS) on epilepsy (n = 12 803 people with epilepsy and 24 218 controls) with that from a GWAS on background EEG (n = 8425 subjects without epilepsy), in which background EEG oscillation power was quantified in four different frequency bands: alpha, beta, delta, and theta. We replicated our findings in an independent epilepsy replication dataset (n = 4851 people with epilepsy and 20 428 controls). To assess the genetic overlap between these phenotypes, we performed genetic correlation analyses using linkage disequilibrium score regression, polygenic risk scores, and Mendelian randomization analyses.ResultsOur analyses show strong genetic correlations of genetic generalized epilepsy (GGE) with background EEG oscillations, primarily in the beta frequency band. Furthermore, we show that subjects with higher beta and theta polygenic risk scores have a significantly higher risk of having generalized epilepsy. Mendelian randomization analyses suggest a causal effect of GGE genetic liability on beta oscillations.SignificanceOur results point to shared biological mechanisms underlying background EEG oscillations and the susceptibility for GGE, opening avenues to investigate the clinical utility of background EEG oscillations in the diagnostic workup of epilepsy.

Published
2021

7. Quantitative analysis of phenotypic elements augments traditional electroclinical classification of common familial epilepsies

Author

Abou‐Khalil, Bassel, Afawi, Zaid, Allen, Andrew S, Bautista, Jocelyn F, Bellows, Susannah T, Berkovic, Samuel F, Bluvstein, Judith, Burgess, Rosemary, Cascino, Gregory, Cossette, Patrick, Cristofaro, Sabrina, Crompton, Douglas E, Delanty, Norman, Devinsky, Orrin, Dlugos, Dennis, Ellis, Colin A, Epstein, Michael P, Fountain, Nathan B, Freyer, Catharine, Geller, Eric B, Glauser, Tracy, Glynn, Simon, Goldberg‐Stern, Hadassa, Goldstein, David B, Gravel, Micheline, Haas, Kevin, Haut, Sheryl, Heinzen, Erin L, Kirsch, Heidi E, Kivity, Sara, Knowlton, Robert, Korczyn, Amos D, Kossoff, Eric, Kuzniecky, Ruben, Loeb, Rebecca, Lowenstein, Daniel H, Marson, Anthony G, McCormack, Mark, McKenna, Kevin, Mefford, Heather C, Motika, Paul, Mullen, Saul A, J. O'Brien, Terence, Ottman, Ruth, Paolicchi, Juliann, Parent, Jack M, Paterson, Sarah, Petrou, Steven, Petrovski, Slavé, Owen Pickrell, William, Poduri, Annapurna, Rees, Mark I, Sadleir, Lynette G, Scheffer, Ingrid E, Shih, Jerry, Singh, Rani, Sirven, Joseph, Smith, Michael, Smith, Phil EM, Thio, Liu Lin, Thomas, Rhys H, Venkat, Anu, Vining, Eileen, Von Allmen, Gretchen, Weisenberg, Judith, Widdess‐Walsh, Peter, and Winawer, Melodie R

Subjects
Neurodegenerative, Neurosciences, Epilepsy, Clinical Research, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Electroencephalography, Epileptic Syndromes, Female, Humans, Latent Class Analysis, Male, Pedigree, Phenotype, epilepsy, genetics, latent class analysis, phenotype, Epi4K Consortium, Clinical Sciences, Neurology & Neurosurgery
Abstract

ObjectiveClassification of epilepsy into types and subtypes is important for both clinical care and research into underlying disease mechanisms. A quantitative, data-driven approach may augment traditional electroclinical classification and shed new light on existing classification frameworks.MethodsWe used latent class analysis, a statistical method that assigns subjects into groups called latent classes based on phenotypic elements, to classify individuals with common familial epilepsies from the Epi4K Multiplex Families study. Phenotypic elements included seizure types, seizure symptoms, and other elements of the medical history. We compared class assignments to traditional electroclinical classifications and assessed familial aggregation of latent classes.ResultsA total of 1120 subjects with epilepsy were assigned to five latent classes. Classes 1 and 2 contained subjects with generalized epilepsy, largely reflecting the distinction between absence epilepsies and younger onset (class 1) versus myoclonic epilepsies and older onset (class 2). Classes 3 and 4 contained subjects with focal epilepsies, and in contrast to classes 1 and 2, these did not adhere as closely to clinically defined focal epilepsy subtypes. Class 5 contained nearly all subjects with febrile seizures plus or unknown epilepsy type, as well as a few subjects with generalized epilepsy and a few with focal epilepsy. Family concordance of latent classes was similar to or greater than concordance of clinically defined epilepsy types.SignificanceQuantitative classification of epilepsy has the potential to augment traditional electroclinical classification by (1) combining some syndromes into a single class, (2) splitting some syndromes into different classes, (3) helping to classify subjects who could not be classified clinically, and (4) defining the boundaries of clinically defined classifications. This approach can guide future research, including molecular genetic studies, by identifying homogeneous sets of individuals that may share underlying disease mechanisms.

Published
2019

8. Ultra-Rare Genetic Variation in the Epilepsies: A Whole-Exome Sequencing Study of 17,606 Individuals

Author

Collaborative, Epi25, Feng, Yen-Chen Anne, Howrigan, Daniel P, Abbott, Liam E, Tashman, Katherine, Cerrato, Felecia, Singh, Tarjinder, Heyne, Henrike, Byrnes, Andrea, Churchhouse, Claire, Watts, Nick, Solomonson, Matthew, Lal, Dennis, Heinzen, Erin L, Dhindsa, Ryan S, Stanley, Kate E, Cavalleri, Gianpiero L, Hakonarson, Hakon, Helbig, Ingo, Krause, Roland, May, Patrick, Weckhuysen, Sarah, Petrovski, Slavé, Kamalakaran, Sitharthan, Sisodiya, Sanjay M, Cossette, Patrick, Cotsapas, Chris, De Jonghe, Peter, Dixon-Salazar, Tracy, Guerrini, Renzo, Kwan, Patrick, Marson, Anthony G, Stewart, Randy, Depondt, Chantal, Dlugos, Dennis J, Scheffer, Ingrid E, Striano, Pasquale, Freyer, Catharine, McKenna, Kevin, Regan, Brigid M, Bellows, Susannah T, Leu, Costin, Bennett, Caitlin A, Johns, Esther MC, Macdonald, Alexandra, Shilling, Hannah, Burgess, Rosemary, Weckhuysen, Dorien, Bahlo, Melanie, O’Brien, Terence J, Todaro, Marian, Stamberger, Hannah, Andrade, Danielle M, Sadoway, Tara R, Mo, Kelly, Krestel, Heinz, Gallati, Sabina, Papacostas, Savvas S, Kousiappa, Ioanna, Tanteles, George A, Štěrbová, Katalin, Vlčková, Markéta, Sedláčková, Lucie, Laššuthová, Petra, Klein, Karl Martin, Rosenow, Felix, Reif, Philipp S, Knake, Susanne, Kunz, Wolfram S, Zsurka, Gábor, Elger, Christian E, Bauer, Jürgen, Rademacher, Michael, Pendziwiat, Manuela, Muhle, Hiltrud, Rademacher, Annika, van Baalen, Andreas, von Spiczak, Sarah, Stephani, Ulrich, Afawi, Zaid, Korczyn, Amos D, Kanaan, Moien, Canavati, Christina, Kurlemann, Gerhard, Müller-Schlüter, Karen, Kluger, Gerhard, Häusler, Martin, Blatt, Ilan, Lemke, Johannes R, Krey, Ilona, Weber, Yvonne G, Wolking, Stefan, Becker, Felicitas, Hengsbach, Christian, Rau, Sarah, Maisch, Ana F, Steinhoff, Bernhard J, Schulze-Bonhage, Andreas, Schubert-Bast, Susanne, and Schreiber, Herbert

Subjects
Clinical Research, Human Genome, Neurosciences, Epilepsy, Biotechnology, Genetics, Neurodegenerative, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Case-Control Studies, DNA Mutational Analysis, Exome, Genetic Markers, Genetic Predisposition to Disease, Genetic Variation, Humans, Phenotype, Exome Sequencing, Epi25 Collaborative. Electronic address: s.berkovic@unimelb.edu.au, Epi25 Collaborative, burden analysis, epilepsy, epileptic encephalopathy, exome, seizures, sequencing, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,436 controls of European ancestry. We focused on three phenotypic groups: severe developmental and epileptic encephalopathies (DEEs), genetic generalized epilepsy (GGE), and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy; we saw the strongest enrichment in individuals with DEEs and the least strong in individuals with NAFE. Moreover, we found that inhibitory GABAA receptor genes were enriched for missense variants across all three classes of epilepsy, whereas no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEEs and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the lead associations; such genes included CACNA1G, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study, the largest epilepsy WES study to date, confirms a convergence in the genetics of severe and less-severe epilepsies associated with ultra-rare coding variation, and it highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology.

Published
2019

9. Missense Variants in the Histone Acetyltransferase Complex Component Gene TRRAP Cause Autism and Syndromic Intellectual Disability.

Author

Cogné, Benjamin, Ehresmann, Sophie, Beauregard-Lacroix, Eliane, Rousseau, Justine, Besnard, Thomas, Garcia, Thomas, Petrovski, Slavé, Avni, Shiri, McWalter, Kirsty, Blackburn, Patrick R, Sanders, Stephan J, Uguen, Kévin, Harris, Jacqueline, Cohen, Julie S, Blyth, Moira, Lehman, Anna, Berg, Jonathan, Li, Mindy H, Kini, Usha, Joss, Shelagh, von der Lippe, Charlotte, Gordon, Christopher T, Humberson, Jennifer B, Robak, Laurie, Scott, Daryl A, Sutton, Vernon R, Skraban, Cara M, Johnston, Jennifer J, Poduri, Annapurna, Nordenskjöld, Magnus, Shashi, Vandana, Gerkes, Erica H, Bongers, Ernie MHF, Gilissen, Christian, Zarate, Yuri A, Kvarnung, Malin, Lally, Kevin P, Kulch, Peggy A, Daniels, Brina, Hernandez-Garcia, Andres, Stong, Nicholas, McGaughran, Julie, Retterer, Kyle, Tveten, Kristian, Sullivan, Jennifer, Geisheker, Madeleine R, Stray-Pedersen, Asbjorg, Tarpinian, Jennifer M, Klee, Eric W, Sapp, Julie C, Zyskind, Jacob, Holla, Øystein L, Bedoukian, Emma, Filippini, Francesca, Guimier, Anne, Picard, Arnaud, Busk, Øyvind L, Punetha, Jaya, Pfundt, Rolph, Lindstrand, Anna, Nordgren, Ann, Kalb, Fayth, Desai, Megha, Ebanks, Ashley Harmon, Jhangiani, Shalini N, Dewan, Tammie, Coban Akdemir, Zeynep H, Telegrafi, Aida, Zackai, Elaine H, Begtrup, Amber, Song, Xiaofei, Toutain, Annick, Wentzensen, Ingrid M, Odent, Sylvie, Bonneau, Dominique, Latypova, Xénia, Deb, Wallid, CAUSES Study, Redon, Sylvia, Bilan, Frédéric, Legendre, Marine, Troyer, Caitlin, Whitlock, Kerri, Caluseriu, Oana, Murphree, Marine I, Pichurin, Pavel N, Agre, Katherine, Gavrilova, Ralitza, Rinne, Tuula, Park, Meredith, Shain, Catherine, Heinzen, Erin L, Xiao, Rui, Amiel, Jeanne, Lyonnet, Stanislas, Isidor, Bertrand, Biesecker, Leslie G, Lowenstein, Dan, Posey, Jennifer E, and Denommé-Pichon, Anne-Sophie

Subjects
CAUSES Study, Deciphering Developmental Disorders study, Humans, Syndrome, Adaptor Proteins, Signal Transducing, Nuclear Proteins, Prognosis, Autistic Disorder, Amino Acid Sequence, Sequence Homology, Mutation, Missense, Adolescent, Adult, Child, Child, Preschool, Infant, Female, Male, Young Adult, Genetic Association Studies, Intellectual Disability, TRRAP, autism spectrum disorder, congenital malformations, de novo variants, histone acetylation, intellectual disability, neurodevelopmental disorders, Intellectual and Developmental Disabilities (IDD), Pediatric, Genetics, Brain Disorders, Neurosciences, Mental Health, Autism, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Mental health, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Acetylation of the lysine residues in histones and other DNA-binding proteins plays a major role in regulation of eukaryotic gene expression. This process is controlled by histone acetyltransferases (HATs/KATs) found in multiprotein complexes that are recruited to chromatin by the scaffolding subunit transformation/transcription domain-associated protein (TRRAP). TRRAP is evolutionarily conserved and is among the top five genes intolerant to missense variation. Through an international collaboration, 17 distinct de novo or apparently de novo variants were identified in TRRAP in 24 individuals. A strong genotype-phenotype correlation was observed with two distinct clinical spectra. The first is a complex, multi-systemic syndrome associated with various malformations of the brain, heart, kidneys, and genitourinary system and characterized by a wide range of intellectual functioning; a number of affected individuals have intellectual disability (ID) and markedly impaired basic life functions. Individuals with this phenotype had missense variants clustering around the c.3127G>A p.(Ala1043Thr) variant identified in five individuals. The second spectrum manifested with autism spectrum disorder (ASD) and/or ID and epilepsy. Facial dysmorphism was seen in both groups and included upslanted palpebral fissures, epicanthus, telecanthus, a wide nasal bridge and ridge, a broad and smooth philtrum, and a thin upper lip. RNA sequencing analysis of skin fibroblasts derived from affected individuals skin fibroblasts showed significant changes in the expression of several genes implicated in neuronal function and ion transport. Thus, we describe here the clinical spectrum associated with TRRAP pathogenic missense variants, and we suggest a genotype-phenotype correlation useful for clinical evaluation of the pathogenicity of the variants.

Published
2019

10. The benefit of diagnostic whole genome sequencing in schizophrenia and other psychotic disorders

Author

Alkelai, Anna, Greenbaum, Lior, Docherty, Anna R., Shabalin, Andrey A., Povysil, Gundula, Malakar, Ayan, Hughes, Daniel, Delaney, Shannon L., Peabody, Emma P., McNamara, James, Gelfman, Sahar, Baugh, Evan H., Zoghbi, Anthony W., Harms, Matthew B., Hwang, Hann-Shyan, Grossman-Jonish, Anat, Aggarwal, Vimla, Heinzen, Erin L., Jobanputra, Vaidehi, Pulver, Ann E., Lerer, Bernard, and Goldstein, David B.

Published
2022
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11. Somatic SLC35A2 variants in the brain are associated with intractable neocortical epilepsy

Author

Winawer, Melodie R, Griffin, Nicole G, Samanamud, Jorge, Baugh, Evan H, Rathakrishnan, Dinesh, Ramalingam, Senthilmurugan, Zagzag, David, Schevon, Catherine A, Dugan, Patricia, Hegde, Manu, Sheth, Sameer A, McKhann, Guy M, Doyle, Werner K, Grant, Gerald A, Porter, Brenda E, Mikati, Mohamad A, Muh, Carrie R, Malone, Colin D, Bergin, Ann Marie R, Peters, Jurriaan M, McBrian, Danielle K, Pack, Alison M, Akman, Cigdem I, LaCoursiere, Christopher M, Keever, Katherine M, Madsen, Joseph R, Yang, Edward, Lidov, Hart GW, Shain, Catherine, Allen, Andrew S, Canoll, Peter D, Crino, Peter B, Poduri, Annapurna H, and Heinzen, Erin L

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Epilepsy, Brain Disorders, Prevention, Human Genome, Neurodegenerative, Genetics, Clinical Research, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Neurological, Adolescent, Brain, Child, Drug Resistant Epilepsy, Exome, Female, Humans, Male, Malformations of Cortical Development, Monosaccharide Transport Proteins, Mutation, Neocortex, Neurons, Phosphatidylinositol 3-Kinases, TOR Serine-Threonine Kinases, Young Adult, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveSomatic variants are a recognized cause of epilepsy-associated focal malformations of cortical development (MCD). We hypothesized that somatic variants may underlie a wider range of focal epilepsy, including nonlesional focal epilepsy (NLFE). Through genetic analysis of brain tissue, we evaluated the role of somatic variation in focal epilepsy with and without MCD.MethodsWe identified somatic variants through high-depth exome and ultra-high-depth candidate gene sequencing of DNA from epilepsy surgery specimens and leukocytes from 18 individuals with NLFE and 38 with focal MCD.ResultsWe observed somatic variants in 5 cases in SLC35A2, a gene associated with glycosylation defects and rare X-linked epileptic encephalopathies. Nonsynonymous variants in SLC35A2 were detected in resected brain, and absent from leukocytes, in 3 of 18 individuals (17%) with NLFE, 1 female and 2 males, with variant allele frequencies (VAFs) in brain-derived DNA of 2 to 14%. Pathologic evaluation revealed focal cortical dysplasia type Ia (FCD1a) in 2 of the 3 NLFE cases. In the MCD cohort, nonsynonymous variants in SCL35A2 were detected in the brains of 2 males with intractable epilepsy, developmental delay, and magnetic resonance imaging suggesting FCD, with VAFs of 19 to 53%; Evidence for FCD was not observed in either brain tissue specimen.InterpretationWe report somatic variants in SLC35A2 as an explanation for a substantial fraction of NLFE, a largely unexplained condition, as well as focal MCD, previously shown to result from somatic mutation but until now only in PI3K-AKT-mTOR pathway genes. Collectively, our findings suggest a larger role than previously recognized for glycosylation defects in the intractable epilepsies. Ann Neurol 2018.

Published
2018

13. Somatic variants as a cause of drug‐resistant epilepsy including mesial temporal lobe epilepsy with hippocampal sclerosis

Author

Carton, Robert J., primary, Doyle, Michael G., additional, Kearney, Hugh, additional, Steward, Charles A., additional, Lench, Nicholas J., additional, Rogers, Anthony, additional, Heinzen, Erin L., additional, McDonald, Seamus, additional, Fay, Joanna, additional, Lacey, Austin, additional, Beausang, Alan, additional, Cryan, Jane, additional, Brett, Francesca, additional, El‐Naggar, Hany, additional, Widdess‐Walsh, Peter, additional, Costello, Daniel, additional, Kilbride, Ronan, additional, Doherty, Colin P., additional, Sweeney, Kieron J., additional, O'Brien, Donncha F., additional, Henshall, David C., additional, Delanty, Norman, additional, Cavalleri, Gianpiero L., additional, and Benson, Katherine A., additional

Published
2024
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15. De Novo Mutations in PPP3CA Cause Severe Neurodevelopmental Disease with Seizures.

Author

Myers, Candace T, Stong, Nicholas, Mountier, Emily I, Helbig, Katherine L, Freytag, Saskia, Sullivan, Joseph E, Ben Zeev, Bruria, Nissenkorn, Andreea, Tzadok, Michal, Heimer, Gali, Shinde, Deepali N, Rezazadeh, Arezoo, Regan, Brigid M, Oliver, Karen L, Ernst, Michelle E, Lippa, Natalie C, Mulhern, Maureen S, Ren, Zhong, Poduri, Annapurna, Andrade, Danielle M, Bird, Lynne M, Bahlo, Melanie, Berkovic, Samuel F, Lowenstein, Daniel H, Scheffer, Ingrid E, Sadleir, Lynette G, Goldstein, David B, Mefford, Heather C, and Heinzen, Erin L

Subjects
Humans, Epilepsy, Spasms, Infantile, Calcineurin, Severity of Illness Index, Cohort Studies, Sequence Analysis, DNA, Synaptic Transmission, Mutation, Adolescent, Adult, Child, Child, Preschool, Infant, Infant, Newborn, Female, Male, Young Adult, Exome, Lennox Gastaut Syndrome, Neurodevelopmental Disorders, PPP3CA, calcineurin, de novo mutation, developmental and epileptic encephalopathy, epilepsy, Brain Disorders, Neurodegenerative, Pediatric, Genetics, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Neurological, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Exome sequencing has readily enabled the discovery of the genetic mutations responsible for a wide range of diseases. This success has been particularly remarkable in the severe epilepsies and other neurodevelopmental diseases for which rare, often de novo, mutations play a significant role in disease risk. Despite significant progress, the high genetic heterogeneity of these disorders often requires large sample sizes to identify a critical mass of individuals with disease-causing mutations in a single gene. By pooling genetic findings across multiple studies, we have identified six individuals with severe developmental delay (6/6), refractory seizures (5/6), and similar dysmorphic features (3/6), each harboring a de novo mutation in PPP3CA. PPP3CA encodes the alpha isoform of a subunit of calcineurin. Calcineurin encodes a calcium- and calmodulin-dependent serine/threonine protein phosphatase that plays a role in a wide range of biological processes, including being a key regulator of synaptic vesicle recycling at nerve terminals. Five individuals with de novo PPP3CA mutations were identified among 4,760 trio probands with neurodevelopmental diseases; this is highly unlikely to occur by chance (p = 1.2 × 10-8) given the size and mutability of the gene. Additionally, a sixth individual with a de novo mutation in PPP3CA was connected to this study through GeneMatcher. Based on these findings, we securely implicate PPP3CA in early-onset refractory epilepsy and further support the emerging role for synaptic dysregulation in epilepsy.

Published
2017

16. Phenotypic analysis of 303 multiplex families with common epilepsies.

Author

Abou-Khalil, Bassel, Afawi, Zaid, Allen, Andrew S, Bautista, Jocelyn F, Bellows, Susannah T, Berkovic, Samuel F, Bluvstein, Judith, Burgess, Rosemary, Cascino, Gregory, Cops, Elisa J, Cossette, Patrick, Cristofaro, Sabrina, Crompton, Douglas E, Delanty, Norman, Devinsky, Orrin, Dlugos, Dennis, Epstein, Michael P, Fountain, Nathan B, Freyer, Catharine, Garry, Sarah I, Geller, Eric B, Glauser, Tracy, Glynn, Simon, Goldberg-Stern, Hadassa, Goldstein, David B, Gravel, Micheline, Haas, Kevin, Haut, Sheryl, Heinzen, Erin L, Kirsch, Heidi E, Kivity, Sara, Knowlton, Robert, Korczyn, Amos D, Kossoff, Eric, Kuzniecky, Ruben, Loeb, Rebecca, Lowenstein, Daniel H, Marson, Anthony G, McCormack, Mark, McKenna, Kevin, Mefford, Heather C, Motika, Paul, Mullen, Saul A, O'Brien, Terence J, Ottman, Ruth, Paolicchi, Juliann, Parent, Jack M, Paterson, Sarah, Petrovski, Slave, Pickrell, William Owen, Poduri, Annapurna, Rees, Mark I, Sadleir, Lynette G, Scheffer, Ingrid E, Shih, Jerry, Singh, Rani, Sirven, Joseph, Smith, Michael, Smith, Phil EM, Thio, Liu Lin, Thomas, Rhys H, Venkat, Anu, Vining, Eileen, Von Allmen, Gretchen, Weisenberg, Judith, Widdess-Walsh, Peter, and Winawer, Melodie R

Subjects
Genetics, Clinical Research, Brain Disorders, Pediatric, Neurosciences, Epilepsy, Neurodegenerative, 2.1 Biological and endogenous factors, Aetiology, Neurological, Adolescent, Age of Onset, Child, Child, Preschool, Epilepsy, Generalized, Family Health, Female, Humans, Male, Pedigree, Phenotype, Sex Factors, Young Adult, epilepsy, multiplex families, phenotype, genetics, Epi4K Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Gene identification in epilepsy has mainly been limited to large families segregating genes of major effect and de novo mutations in epileptic encephalopathies. Many families that present with common non-acquired focal epilepsies and genetic generalized epilepsies remain unexplained. We assembled a cohort of 'genetically enriched' common epilepsies by collecting and phenotyping families containing multiple individuals with unprovoked seizures. We aimed to determine if specific clinical epilepsy features aggregate within families, and whether this segregation of phenotypes may constitute distinct 'familial syndromes' that could inform genomic analyses. Families with three or more individuals with unprovoked seizures were studied across multiple international centres. Affected individuals were phenotyped and classified according to specific electroclinical syndromes. Families were categorized based on syndromic groupings of affected family members, examined for pedigree structure and phenotypic patterns and, where possible, assigned specific familial epilepsy syndromes. A total of 303 families were assembled and analysed, comprising 1120 affected phenotyped individuals. Of the 303 families, 117 exclusively segregated generalized epilepsy, 62 focal epilepsy, and 22 were classified as genetic epilepsy with febrile seizures plus. Over one-third (102 families) were observed to have mixed epilepsy phenotypes: 78 had both generalized and focal epilepsy features within the same individual (n = 39), or within first or second degree relatives (n = 39). Among the genetic generalized epilepsy families, absence epilepsies were found to cluster within families independently of juvenile myoclonic epilepsy, and significantly more females were affected than males. Of the 62 familial focal epilepsy families, two previously undescribed familial focal syndrome patterns were evident: 15 families had posterior quadrant epilepsies, including seven with occipito-temporal localization and seven with temporo-parietal foci, and four families displayed familial focal epilepsy of childhood with multiple affected siblings that was suggestive of recessive inheritance. The findings suggest (i) specific patterns of syndromic familial aggregation occur, including newly recognized forms of familial focal epilepsy; (ii) although syndrome-specificity usually occurs in multiplex families, the one-third of families with features of both focal and generalized epilepsy is suggestive of shared genetic determinants; and (iii) patterns of features observed across families including pedigree structure, sex, and age of onset may hold clues for future gene identification. Such detailed phenotypic information will be invaluable in the conditioning and interpretation of forthcoming sequencing data to understand the genetic architecture and inter-relationships of the common epilepsy syndromes.

Published
2017

17. A case-control collapsing analysis identifies epilepsy genes implicated in trio sequencing studies focused on de novo mutations

Author

Zhu, Xiaolin, Padmanabhan, Raghavendra, Copeland, Brett, Bridgers, Joshua, Ren, Zhong, Kamalakaran, Sitharthan, O'Driscoll-Collins, Ailbhe, Berkovic, Samuel F, Scheffer, Ingrid E, Poduri, Annapurna, Mei, Davide, Guerrini, Renzo, Lowenstein, Daniel H, Allen, Andrew S, Heinzen, Erin L, and Goldstein, David B

Subjects
Biological Sciences, Genetics, Neurodegenerative, Biotechnology, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Case-Control Studies, DNA Mutational Analysis, Epilepsy, Female, Genes, Dominant, Genome-Wide Association Study, Humans, Male, Munc18 Proteins, Mutation, NAV1.2 Voltage-Gated Sodium Channel, Nerve Tissue Proteins, Potassium Channels, Potassium Channels, Sodium-Activated, Exome Sequencing, Developmental Biology
Abstract

Trio exome sequencing has been successful in identifying genes with de novo mutations (DNMs) causing epileptic encephalopathy (EE) and other neurodevelopmental disorders. Here, we evaluate how well a case-control collapsing analysis recovers genes causing dominant forms of EE originally implicated by DNM analysis. We performed a genome-wide search for an enrichment of "qualifying variants" in protein-coding genes in 488 unrelated cases compared to 12,151 unrelated controls. These "qualifying variants" were selected to be extremely rare variants predicted to functionally impact the protein to enrich for likely pathogenic variants. Despite modest sample size, three known EE genes (KCNT1, SCN2A, and STXBP1) achieved genome-wide significance (p

Published
2017

20. RNA methyltransferase SPOUT1/CENP-32 links mitotic spindle organization with the neurodevelopmental disorder SpADMiSS

Author

Dharmadhikari, Avinash V, primary, Abad, Maria Alba, additional, Khan, Sheraz, additional, Maroofian, Reza, additional, Sands, Tristan T, additional, Ullah, Farid, additional, Samejima, Itaru, additional, Wear, Martin A, additional, Moore, Kiara E, additional, Kondakova, Elena, additional, Mitina, Natalia, additional, Schaub, Theres, additional, Lee, Grace K, additional, Umandap, Christine H, additional, Berger, Sara M, additional, Iglesias, Alejandro D, additional, Popp, Bernt, additional, Jamra, Rami Abou, additional, Gabriel, Heinz, additional, Rentas, Stefan, additional, Rippert, Alyssa L, additional, Izumi, Kosuke, additional, Conlin, Laura K, additional, Koboldt, Daniel C, additional, Mihalic Mosher, Theresa, additional, Hickey, Scott E, additional, Albert, Dara VF, additional, Norwood, Haley, additional, Lewanda, Amy Feldman, additional, Dai, Hongzheng, additional, Liu, Pengfei, additional, Mitani, Tadahiro, additional, Marafi, Dana, additional, Pehlivan, Davut, additional, Posey, Jennifer E, additional, Lippa, Natalie, additional, Vena, Natalie, additional, Heinzen, Erin L, additional, Goldstein, David B, additional, Mignot, Cyril, additional, Agathe, Jean-Madeleine de Sainte, additional, Al-Sannaa, Nouriya Abbas, additional, Zamani, Mina, additional, Sadeghian, Saeid, additional, Seifia, Tahere, additional, Zaki, Maha S, additional, Abdel-Salam, Ghada MH, additional, Abdel-Hamid, Mohamed, additional, Alabdi, Lama, additional, Alkuraya, Fowzan Sami, additional, Dawoud, Heba, additional, Lofty, Aya, additional, Bauer, Peter, additional, Zifarelli, Giovanni, additional, Afzal, Erum, additional, Zafar, Faisal, additional, Efthymiou, Stephanie, additional, Gossett, Daniel, additional, Towne, Meghan C, additional, Yeneabat, Raey, additional, Wontakal, Sandeep N, additional, Aggarwal, Vimla S, additional, Rosenfeld, Jill A, additional, Tarabykin, Victor, additional, Ohta, Shinya, additional, Lupski, James R, additional, Houlden, Henry, additional, Earnshaw, William C, additional, Davis, Erica E, additional, Jeyaprakash, A Arockia, additional, and Liao, Jun, additional

Published
2024
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21. De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies

Author

Consortium, Epi4K, Myers, Candace T, McMahon, Jacinta M, Schneider, Amy L, Petrovski, Slavé, Allen, Andrew S, Carvill, Gemma L, Zemel, Matthew, Saykally, Julia E, LaCroix, Amy J, Heinzen, Erin L, Hollingsworth, Georgina, Nikanorova, Marina, Corbett, Mark, Gecz, Jozef, Coman, David, Freeman, Jeremy, Calvert, Sophie, Gill, Deepak, Carney, Patrick, Lerman-Sagie, Tally, Sampaio, Hugo, Cossette, Patrick, Delanty, Norman, Dlugos, Dennis, Eichler, Evan E, Epstein, Michael P, Glauser, Tracy, Johnson, Michael R, Kuzniecky, Ruben, Marson, Anthony G, O’Brien, Terence J, Ottman, Ruth, Petrou, Stephen, Poduri, Annapurna, Pickrell, William O, Chung, Seo-Kyung, Rees, Mark I, Sherr, Elliott, Sadleir, Lynette G, Goldstein, David B, Lowenstein, Daniel H, Møller, Rikke S, Berkovic, Samuel F, Scheffer, Ingrid E, and Mefford, Heather C

Subjects
Human Genome, Brain Disorders, Pediatric, Prevention, Genetics, Aetiology, 2.1 Biological and endogenous factors, Adolescent, Adult, Alleles, Calcium Channels, Child, Preschool, Cohort Studies, Epilepsy, Excitatory Amino Acid Transporter 2, Female, GTP-Binding Protein alpha Subunits, Gi-Go, Glutamate Plasma Membrane Transport Proteins, Guanine Nucleotide Exchange Factors, Humans, Infant, Infant, Newborn, Male, Mosaicism, Mutation, N-Acetylglucosaminyltransferases, Receptors, GABA-A, Seizures, Epi4K Consortium, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Epileptic encephalopathies (EEs) are the most clinically important group of severe early-onset epilepsies. Next-generation sequencing has highlighted the crucial contribution of de novo mutations to the genetic architecture of EEs as well as to their underlying genetic heterogeneity. Our previous whole-exome sequencing study of 264 parent-child trios revealed more than 290 candidate genes in which only a single individual had a de novo variant. We sought to identify additional pathogenic variants in a subset (n = 27) of these genes via targeted sequencing in an unsolved cohort of 531 individuals with a diverse range of EEs. We report 17 individuals with pathogenic variants in seven of the 27 genes, defining a genetic etiology in 3.2% of this unsolved cohort. Our results provide definitive evidence that de novo mutations in SLC1A2 and CACNA1A cause specific EEs and expand the compendium of clinically relevant genotypes for GABRB3. We also identified EEs caused by genetic variants in ALG13, DNM1, and GNAO1 and report a mutation in IQSEC2. Notably, recurrent mutations accounted for 7/17 of the pathogenic variants identified. As a result of high-depth coverage, parental mosaicism was identified in two out of 14 cases tested with mutant allelic fractions of 5%-6% in the unaffected parents, carrying significant reproductive counseling implications. These results confirm that dysregulation in diverse cellular neuronal pathways causes EEs, and they will inform the diagnosis and management of individuals with these devastating disorders.

Published
2016

23. Copy number variant analysis from exome data in 349 patients with epileptic encephalopathy

Author

Allen, Andrew S, Berkovic, Samuel F, Coe, Bradley P, Cook, Joseph, Cossette, Patrick, Delanty, Norman, Dlugos, Dennis, Eichler, Evan E, Epstein, Michael P, Glauser, Tracy, Goldstein, David B, Heinzen, Erin L, Johnson, Michael R, Krumm, Nik, Kuzniecky, Ruben, Lowenstein, Daniel H, Marson, Anthony G, Mefford, Heather C, Nelson, Ben, Esmaeeli Nieh, Sahar, O'Brien, Terence J, Ottman, Ruth, Petrou, Stephen, Petrovski, Slavé, Poduri, Annapurna, Raja, Archana, Ruzzo, Elizabeth K, Scheffer, Ingrid E, Sherr, Elliott, Abou‐Khalil, Bassel, Alldredge, Brian K, Andermann, Eva, Andermann, Frederick, Amron, Dina, Bautista, Jocelyn F, Boro, Alex, Cascino, Gregory, Consalvo, Damian, Crumrine, Patricia, Devinsky, Orrin, Fiol, Miguel, Fountain, Nathan B, French, Jacqueline, Friedman, Daniel, Geller, Eric B, Glynn, Simon, Haut, Sheryl R, Hayward, Jean, Helmers, Sandra L, Joshi, Sucheta, Kanner, Andres, Kirsch, Heidi E, Knowlton, Robert C, Kossoff, Eric H, Kuperman, Rachel, McGuire, Shannon M, Motika, Paul V, Novotny, Edward J, Paolicchi, Juliann M, Parent, Jack, Park, Kristen, Shellhaas, Renée A, Shih, Jerry J, Singh, Rani, Sirven, Joseph, Smith, Michael C, Sullivan, Joe, Thio, Liu Lin, Venkat, Anu, Vining, Eileen PG, Von Allmen, Gretchen K, Weisenberg, Judith L, Widdess‐Walsh, Peter, and Winawer, Melodie R

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Neurodegenerative, Genetics, Intellectual and Developmental Disabilities (IDD), Epilepsy, Pediatric, Clinical Research, Brain Disorders, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Adult, Child, Preschool, Cohort Studies, DNA Copy Number Variations, Exome, Female, Humans, Infant, Infant, Newborn, Lennox Gastaut Syndrome, Male, Parents, Sequence Analysis, DNA, Spasms, Infantile, Epilepsy Phenome/Genome Project Epi4K Consortium, Neurology & Neurosurgery, Clinical sciences
Abstract

Infantile spasms (IS) and Lennox-Gastaut syndrome (LGS) are epileptic encephalopathies characterized by early onset, intractable seizures, and poor developmental outcomes. De novo sequence mutations and copy number variants (CNVs) are causative in a subset of cases. We used exome sequence data in 349 trios with IS or LGS to identify putative de novo CNVs. We confirm 18 de novo CNVs in 17 patients (4.8%), 10 of which are likely pathogenic, giving a firm genetic diagnosis for 2.9% of patients. Confirmation of exome-predicted CNVs by array-based methods is still required due to false-positive rates of prediction algorithms. Our exome-based results are consistent with recent array-based studies in similar cohorts and highlight novel candidate genes for IS and LGS.

Published
2015

24. New insights into tardive dyskinesia genetics: Implementation of whole-exome sequencing approach

Author

Alkelai, Anna, Greenbaum, Lior, Heinzen, Erin L., Baugh, Evan H., Teitelbaum, Alexander, Zhu, Xiaolin, Strous, Rael D., Tatarskyy, Pavel, Zai, Clement C., Tiwari, Arun K., Tampakeras, Maria, Freeman, Natalie, Müller, Daniel J., Voineskos, Aristotle N., Lieberman, Jeffrey A., Delaney, Shannon L., Meltzer, Herbert Y., Remington, Gary, Kennedy, James L., Pulver, Ann E., Peabody, Emma P., Levy, Deborah L., and Lerer, Bernard

Published
2019
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25. SLC25A22 is a novel gene for migrating partial seizures in infancy

Author

Poduri, Annapurna, Heinzen, Erin L, Chitsazzadeh, Vida, Lasorsa, Francesco Massimo, Elhosary, P Christina, LaCoursiere, Christopher M, Martin, Emilie, Yuskaitis, Christopher J, Hill, Robert Sean, Atabay, Kutay Deniz, Barry, Brenda, Partlow, Jennifer N, Bashiri, Fahad A, Zeidan, Radwan M, Elmalik, Salah A, Kabiraj, Mohammad MU, Kothare, Sanjeev, Stödberg, Tommy, McTague, Amy, Kurian, Manju A, Scheffer, Ingrid E, Barkovich, A James, Palmieri, Ferdinando, Salih, Mustafa A, and Walsh, Christopher A

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Genetics, Neurodegenerative, Human Genome, Biotechnology, Brain Disorders, Epilepsy, Clinical Research, Pediatric, 2.1 Biological and endogenous factors, Aetiology, Neurological, Adult, Consanguinity, Epilepsy, Benign Neonatal, Exome, Female, Genetic Linkage, Humans, Infant, Newborn, Male, Mitochondrial Membrane Transport Proteins, Pedigree, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveTo identify a genetic cause for migrating partial seizures in infancy (MPSI).MethodsWe characterized a consanguineous pedigree with MPSI and obtained DNA from affected and unaffected family members. We analyzed single nucleotide polymorphism 500K data to identify regions with evidence of linkage. We performed whole exome sequencing and analyzed homozygous variants in regions of linkage to identify a candidate gene and performed functional studies of the candidate gene SLC25A22.ResultsIn a consanguineous pedigree with 2 individuals with MPSI, we identified 2 regions of linkage, chromosome 4p16.1-p16.3 and chromosome 11p15.4-pter. Using whole exome sequencing, we identified 8 novel homozygous variants in genes in these regions. Only 1 variant, SLC25A22 c.G328C, results in a change of a highly conserved amino acid (p.G110R) and was not present in control samples. SLC25A22 encodes a glutamate transporter with strong expression in the developing brain. We show that the specific G110R mutation, located in a transmembrane domain of the protein, disrupts mitochondrial glutamate transport.InterpretationWe have shown that MPSI can be inherited and have identified a novel homozygous mutation in SLC25A22 in the affected individuals. Our data strongly suggest that SLC25A22 is responsible for MPSI, a severe condition with few known etiologies. We have demonstrated that a combination of linkage analysis and whole exome sequencing can be used for disease gene discovery. Finally, as SLC25A22 had been implicated in the distinct syndrome of neonatal epilepsy with suppression bursts on electroencephalogram, we have expanded the phenotypic spectrum associated with SLC25A22.

Published
2013

27. The copy number variation landscape of congenital anomalies of the kidney and urinary tract

Author

Verbitsky, Miguel, Westland, Rik, Perez, Alejandra, Kiryluk, Krzysztof, Liu, Qingxue, Krithivasan, Priya, Mitrotti, Adele, Fasel, David A., Batourina, Ekaterina, Sampson, Matthew G., Bodria, Monica, Werth, Max, Kao, Charlly, Martino, Jeremiah, Capone, Valentina P., Vivante, Asaf, Shril, Shirlee, Kil, Byum Hee, Marasà, Maddalena, Zhang, Jun Y., Na, Young-Ji, Lim, Tze Y., Ahram, Dina, Weng, Patricia L., Heinzen, Erin L., Carrea, Alba, Piaggio, Giorgio, Gesualdo, Loreto, Manca, Valeria, Masnata, Giuseppe, Gigante, Maddalena, Cusi, Daniele, Izzi, Claudia, Scolari, Francesco, van Wijk, Joanna A. E., Saraga, Marijan, Santoro, Domenico, Conti, Giovanni, Zamboli, Pasquale, White, Hope, Drozdz, Dorota, Zachwieja, Katarzyna, Miklaszewska, Monika, Tkaczyk, Marcin, Tomczyk, Daria, Krakowska, Anna, Sikora, Przemyslaw, Jarmoliński, Tomasz, Borszewska-Kornacka, Maria K., Pawluch, Robert, Szczepanska, Maria, Adamczyk, Piotr, Mizerska-Wasiak, Malgorzata, Krzemien, Grazyna, Szmigielska, Agnieszka, Zaniew, Marcin, Dobson, Mark G., Darlow, John M., Puri, Prem, Barton, David E., Furth, Susan L., Warady, Bradley A., Gucev, Zoran, Lozanovski, Vladimir J., Tasic, Velibor, Pisani, Isabella, Allegri, Landino, Rodas, Lida M., Campistol, Josep M., Jeanpierre, Cécile, Alam, Shumyle, Casale, Pasquale, Wong, Craig S., Lin, Fangming, Miranda, Débora M., Oliveira, Eduardo A., Simões-e-Silva, Ana Cristina, Barasch, Jonathan M., Levy, Brynn, Wu, Nan, Hildebrandt, Friedhelm, Ghiggeri, Gian Marco, Latos-Bielenska, Anna, Materna-Kiryluk, Anna, Zhang, Feng, Hakonarson, Hakon, Papaioannou, Virginia E., Mendelsohn, Cathy L., Gharavi, Ali G., and Sanna-Cherchi, Simone

Published
2019
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29. Contribution of Somatic Ras/Raf/Mitogen-Activated Protein Kinase Variants in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy

Author

Khoshkhoo, Sattar, primary, Wang, Yilan, additional, Chahine, Yasmine, additional, Erson-Omay, E. Zeynep, additional, Robert, Stephanie M., additional, Kiziltug, Emre, additional, Damisah, Eyiyemisi C., additional, Nelson-Williams, Carol, additional, Zhu, Guangya, additional, Kong, Wenna, additional, Huang, August Yue, additional, Stronge, Edward, additional, Phillips, H. Westley, additional, Chhouk, Brian H., additional, Bizzotto, Sara, additional, Chen, Ming Hui, additional, Adikari, Thiuni N., additional, Ye, Zimeng, additional, Witkowski, Tom, additional, Lai, Dulcie, additional, Lee, Nadine, additional, Lokan, Julie, additional, Scheffer, Ingrid E., additional, Berkovic, Samuel F., additional, Haider, Shozeb, additional, Hildebrand, Michael S., additional, Yang, Edward, additional, Gunel, Murat, additional, Lifton, Richard P., additional, Richardson, R. Mark, additional, Blümcke, Ingmar, additional, Alexandrescu, Sanda, additional, Huttner, Anita, additional, Heinzen, Erin L., additional, Zhu, Jidong, additional, Poduri, Annapurna, additional, DeLanerolle, Nihal, additional, Spencer, Dennis D., additional, Lee, Eunjung Alice, additional, Walsh, Christopher A., additional, and Kahle, Kristopher T., additional

Published
2023
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31. Mosaic variants detectable in blood extend the clinico-genetic spectrum of GLI3-related Hypothalamic Hamartoma

Author

Green, Timothy E., primary, Bennett, Mark F., additional, Immisch, Ilka, additional, Freeman, Jeremy L., additional, Klein, Karl Martin, additional, Kerrigan, John F., additional, Vadlamudi, Lata, additional, Heinzen, Erin L., additional, Scheffer, Ingrid E., additional, Harvey, A. Simon, additional, Rosenow, Felix, additional, Hildebrand, Michael S., additional, and Berkovic, Samuel F., additional

Published
2023
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32. Somatic Ras/Raf/MAPK Variants Enriched in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy

Author

Khoshkhoo, Sattar, primary, Wang, Yilan, additional, Chahine, Yasmine, additional, Erson-Omay, E. Zeynep, additional, Robert, Stephanie, additional, Kiziltug, Emre, additional, Damisah, Eyiyemisi C., additional, Nelson-Williams, Carol, additional, Zhu, Guangya, additional, Kong, Wenna, additional, Huang, August Yue, additional, Stronge, Edward, additional, Phillips, H. Westley, additional, Chhouk, Brian H., additional, Bizzotto, Sara, additional, Chen, Ming Hui, additional, Adikari, Thiuni N., additional, Ye, Zimeng, additional, Witkowski, Tom, additional, Lai, Dulcie, additional, Lee, Nadine, additional, Lokan, Julie, additional, Scheffer, Ingrid E., additional, Berkovic, Samuel F., additional, Haider, Shozeb, additional, Hildebrand, Michael S., additional, Yang, Edward, additional, Gunel, Murat, additional, Lifton, Richard P., additional, Richardson, R Mark, additional, Blümcke, Ingmar, additional, Alexandrescu, Sanda, additional, Huttner, Anita, additional, Heinzen, Erin L., additional, Zhu, Jidong, additional, Poduri, Annapurna, additional, DeLanerolle, Nihal, additional, Spencer, Dennis D., additional, Lee, Eunjung Alice, additional, Walsh, Christopher A., additional, and Kahle, Kristopher T., additional

Published
2022
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34. Distinct neurological disorders with ATP1A3 mutations

Author

Heinzen, Erin L, Arzimanoglou, Alexis, Brashear, Allison, Clapcote, Steven J, Gurrieri, Fiorella, Goldstein, David B, Jóhannesson, Sigurður H, Mikati, Mohamad A, Neville, Brian, Nicole, Sophie, Ozelius, Laurie J, Poulsen, Hanne, Schyns, Tsveta, Sweadner, Kathleen J, van den Maagdenberg, Arn, and Vilsen, Bente

Published
2014
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35. Gaps and opportunities in refractory status epilepticus research in children: A multi-center approach by the Pediatric Status Epilepticus Research Group (pSERG)

Author

Sánchez Fernández, Iván, Abend, Nicholas S., Agadi, Satish, An, Sookee, Arya, Ravindra, Carpenter, Jessica L., Chapman, Kevin E., Gaillard, William D., Glauser, Tracy A., Goldstein, David B., Goldstein, Joshua L., Goodkin, Howard P., Hahn, Cecil D., Heinzen, Erin L., Mikati, Mohamad A., Peariso, Katrina, Pestian, John P., Ream, Margie, Riviello, James J., Jr., Tasker, Robert C., Williams, Korwyn, and Loddenkemper, Tobias

Published
2014
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36. Common risk variants for epilepsy are enriched in families previously targeted for rare monogenic variant discovery

Author

Oliver, Karen L., primary, Ellis, Colin A., additional, Scheffer, Ingrid E., additional, Ganesan, Shiva, additional, Leu, Costin, additional, Sadleir, Lynette G., additional, Heinzen, Erin L., additional, Mefford, Heather C., additional, Bass, Andrew J., additional, Curtis, Sarah W., additional, Harris, Rebekah V., additional, Whiteman, David C., additional, Helbig, Ingo, additional, Ottman, Ruth, additional, Epstein, Michael P., additional, Bahlo, Melanie, additional, and Berkovic, Samuel F., additional

Published
2022
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38. A pharmacogenomic assessment of psychiatric adverse drug reactions to levetiracetam.

Author

Campbell, Ciarán, McCormack, Mark, Patel, Sonn, Stapleton, Caragh, Bobbili, Dheeraj Reddy, Krause, Roland, Depondt, Chantal, Sills, Graeme J., Koeleman, Bobby P., Striano, Pasquale, Zara, Federico, Sander, Josemir W., Lerche, Holger, Kunz, Wolfram S., Stefansson, Kari, Stefansson, Hreinn, Doherty, Colin P., Heinzen, Erin L., Scheffer, Ingrid E., Goldstein, David B., O'Brien, Terence, Cotter, David, Berkovic, Samuel F., Sisodiya, Sanjay M., Delanty, Norman, Cavalleri, Gianpiero L., Campbell, Ciarán, McCormack, Mark, Patel, Sonn, Stapleton, Caragh, Bobbili, Dheeraj Reddy, Krause, Roland, Depondt, Chantal, Sills, Graeme J., Koeleman, Bobby P., Striano, Pasquale, Zara, Federico, Sander, Josemir W., Lerche, Holger, Kunz, Wolfram S., Stefansson, Kari, Stefansson, Hreinn, Doherty, Colin P., Heinzen, Erin L., Scheffer, Ingrid E., Goldstein, David B., O'Brien, Terence, Cotter, David, Berkovic, Samuel F., Sisodiya, Sanjay M., Delanty, Norman, and Cavalleri, Gianpiero L.

Abstract

OBJECTIVE: Levetiracetam (LEV) is an effective antiseizure medicine, but 10%-20% of people treated with LEV report psychiatric side-effects, and up to 1% may have psychotic episodes. Pharmacogenomic predictors of these adverse drug reactions (ADRs) have yet to be identified. We sought to determine the contribution of both common and rare genetic variation to psychiatric and behavioral ADRs associated with LEV. METHODS: This case-control study compared cases of LEV-associated behavioral disorder (n = 149) or psychotic reaction (n = 37) to LEV-exposed people with no history of psychiatric ADRs (n = 920). All samples were of European ancestry. We performed genome-wide association study (GWAS) analysis comparing those with LEV ADRs to controls. We estimated the polygenic risk scores (PRS) for schizophrenia and compared cases with LEV-associated psychotic reaction to controls. Rare variant burden analysis was performed using exome sequence data of cases with psychotic reactions (n = 18) and controls (n = 122). RESULTS: Univariate GWAS found no significant associations with either LEV-associated behavioural disorder or LEV-psychotic reaction. PRS analysis showed that cases of LEV-associated psychotic reaction had an increased PRS for schizophrenia relative to contr ols (p = .0097, estimate = .4886). The rare-variant analysis found no evidence of an increased burden of rare genetic variants in people who had experienced LEV-associated psychotic reaction relative to controls. SIGNIFICANCE: The polygenic burden for schizophrenia is a risk factor for LEV-associated psychotic reaction. To assess the clinical utility of PRS as a predictor, it should be tested in an independent and ideally prospective cohort. Larger sample sizes are required for the identification of significant univariate common genetic signals or rare genetic signals associated with psychiatric LEV ADRs.

Published
2022

39. Rare Genetic Variation and Outcome of Surgery for Mesial Temporal Lobe Epilepsy.

Author

Perucca, Piero, Stanley, Kate, Harris, Nicola N.J., McIntosh, Anne AM, Asadi-Pooya, Ali AA, Mikati, Mohamad A, Andrade, Danielle, Dugan, Patricia, Depondt, Chantal, Choi, Hyunmi, Heinzen, Erin L, Cavalleri, Gianpiero L, Buono, Russell J, Devinsky, Orrin In, Sperling, Michael MR, Berkovic, Samuel F, Delanty, Norman, Goldstein, David B, O'Brien, Terence, EPIGEN Consortium, Perucca, Piero, Stanley, Kate, Harris, Nicola N.J., McIntosh, Anne AM, Asadi-Pooya, Ali AA, Mikati, Mohamad A, Andrade, Danielle, Dugan, Patricia, Depondt, Chantal, Choi, Hyunmi, Heinzen, Erin L, Cavalleri, Gianpiero L, Buono, Russell J, Devinsky, Orrin In, Sperling, Michael MR, Berkovic, Samuel F, Delanty, Norman, Goldstein, David B, O'Brien, Terence, and EPIGEN Consortium

Abstract

Genetic factors have long been debated as a cause of failure of surgery for mesial temporal lobe epilepsy (MTLE). We investigated whether rare genetic variation influences seizure outcomes of MTLE surgery., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2022

40. Reply

Author

Depondt, Chantal, Heinzen, Erin L., and Goldstein, David B.

Published
2017
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41. Rare Genetic Variation and Outcome of Surgery for Mesial Temporal Lobe Epilepsy.

Author

Perucca, Piero, Stanley, Kate, Harris, Natasha, McIntosh, Anne M., Asadi‐Pooya, Ali A., Mikati, Mohamad A., Andrade, Danielle M., Dugan, Patricia, Depondt, Chantal, Choi, Hyunmi, Heinzen, Erin L., Cavalleri, Gianpiero L., Buono, Russell J., Devinsky, Orrin, Sperling, Michael R., Berkovic, Samuel F., Delanty, Norman, Goldstein, David B., O'Brien, Terence J., and Andrade, Danielle

Subjects
TEMPORAL lobe epilepsy, TEMPORAL lobectomy, GENETIC variation, HIPPOCAMPAL sclerosis, MAGNETIC resonance imaging, MISSENSE mutation
Abstract

Objective: Genetic factors have long been debated as a cause of failure of surgery for mesial temporal lobe epilepsy (MTLE). We investigated whether rare genetic variation influences seizure outcomes of MTLE surgery. Methods: We performed an international, multicenter, whole exome sequencing study of patients who underwent surgery for drug‐resistant, unilateral MTLE with normal magnetic resonance imaging (MRI) or MRI evidence of hippocampal sclerosis and ≥2‐year postsurgical follow‐up. Patients with either sustained seizure freedom (favorable outcome) or ongoing uncontrolled seizures since surgery (unfavorable outcome) were included. Exomes of controls without epilepsy were also included. Gene set burden analyses were carried out to identify genes with significant enrichment of rare deleterious variants in patients compared to controls. Results: Nine centers from 3 continents contributed 206 patients operated for drug‐resistant unilateral MTLE, of whom 196 (149 with favorable outcome and 47 with unfavorable outcome) were included after stringent quality control. Compared to 8,718 controls, MTLE cases carried a higher burden of ultrarare missense variants in constrained genes that are intolerant to loss‐of‐function (LoF) variants (odds ratio [OR] = 2.6, 95% confidence interval [CI] = 1.9–3.5, p = 1.3E‐09) and in genes encoding voltage‐gated cation channels (OR = 2.4, 95% CI = 1.4–3.8, p = 2.7E‐04). Proportions of subjects with such variants were comparable between patients with favorable outcome and those with unfavorable outcome, with no significant between‐group differences. Interpretation: Rare variation contributes to the genetic architecture of MTLE, but does not appear to have a major role in failure of MTLE surgery. These findings can be incorporated into presurgical decision‐making and counseling. ANN NEUROL 2023;93:752–761 [ABSTRACT FROM AUTHOR]

Published
2023
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42. Author Correction: The copy number variation landscape of congenital anomalies of the kidney and urinary tract

Author

Verbitsky, Miguel, Westland, Rik, Perez, Alejandra, Kiryluk, Krzysztof, Liu, Qingxue, Krithivasan, Priya, Mitrotti, Adele, Fasel, David A., Batourina, Ekaterina, Sampson, Matthew G., Bodria, Monica, Werth, Max, Kao, Charlly, Martino, Jeremiah, Capone, Valentina P., Vivante, Asaf, Shril, Shirlee, Kil, Byum Hee, Marasa, Maddalena, Zhang, Jun Y., Na, Young-Ji, Lim, Tze Y., Ahram, Dina, Weng, Patricia L., Heinzen, Erin L., Carrea, Alba, Piaggio, Giorgio, Gesualdo, Loreto, Manca, Valeria, Masnata, Giuseppe, Gigante, Maddalena, Cusi, Daniele, Izzi, Claudia, Scolari, Francesco, van Wijk, Joanna A. E., Saraga, Marijan, Santoro, Domenico, Conti, Giovanni, Zamboli, Pasquale, White, Hope, Drozdz, Dorota, Zachwieja, Katarzyna, Miklaszewska, Monika, Tkaczyk, Marcin, Tomczyk, Daria, Krakowska, Anna, Sikora, Przemyslaw, Jarmoliński, Tomasz, Borszewska-Kornacka, Maria K., Pawluch, Robert, Szczepanska, Maria, Adamczyk, Piotr, Mizerska-Wasiak, Malgorzata, Krzemien, Grazyna, Szmigielska, Agnieszka, Zaniew, Marcin, Dobson, Mark G., Darlow, John M., Puri, Prem, Barton, David E., Furth, Susan L., Warady, Bradley A., Gucev, Zoran, Lozanovski, Vladimir J., Tasic, Velibor, Pisani, Isabella, Allegri, Landino, Rodas, Lida M., Campistol, Josep M., Jeanpierre, Cécile, Alam, Shumyle, Casale, Pasquale, Wong, Craig S., Lin, Fangming, Miranda, Débora M., Oliveira, Eduardo A., Simoes-e-Silva, Ana Cristina, Barasch, Jonathan M., Levy, Brynn, Wu, Nan, Hildebrandt, Friedhelm, Ghiggeri, Gian Marco, Latos-Bielenska, Anna, Materna-Kiryluk, Anna, Zhang, Feng, Hakonarson, Hakon, Papaioannou, Virginia E., Mendelsohn, Cathy L., Gharavi, Ali G., and Sanna-Cherchi, Simone

Published
2019
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43. Somatic variants in diverse genes leads to a spectrum of focal cortical malformations

Author

Lai, Dulcie, primary, Gade, Meethila, additional, Yang, Edward, additional, Koh, Hyun Yong, additional, Lu, Jinfeng, additional, Walley, Nicole M, additional, Buckley, Anne F, additional, Sands, Tristan T, additional, Akman, Cigdem I, additional, Mikati, Mohamad A, additional, McKhann, Guy M, additional, Goldman, James E, additional, Canoll, Peter, additional, Alexander, Allyson L, additional, Park, Kristen L, additional, Von Allmen, Gretchen K, additional, Rodziyevska, Olga, additional, Bhattacharjee, Meenakshi B, additional, Lidov, Hart G W, additional, Vogel, Hannes, additional, Grant, Gerald A, additional, Porter, Brenda E, additional, Poduri, Annapurna H, additional, Crino, Peter B, additional, and Heinzen, Erin L, additional

Published
2022
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45. Sporadic hypothalamic hamartoma is a ciliopathy with somatic and bi-allelic contributions

Author

Green, Timothy E, primary, Motelow, Joshua E, additional, Bennett, Mark F, additional, Ye, Zimeng, additional, Bennett, Caitlin A, additional, Griffin, Nicole G, additional, Damiano, John A, additional, Leventer, Richard J, additional, Freeman, Jeremy L, additional, Harvey, A Simon, additional, Lockhart, Paul J, additional, Sadleir, Lynette G, additional, Boys, Amber, additional, Scheffer, Ingrid E, additional, Major, Heather, additional, Darbro, Benjamin W, additional, Bahlo, Melanie, additional, Goldstein, David B, additional, Kerrigan, John F, additional, Heinzen, Erin L, additional, Berkovic, Samuel F, additional, and Hildebrand, Michael S, additional

Published
2022
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46. Somatic mutation involving diverse genes leads to a spectrum of focal cortical malformations

Author

Lai, Dulcie, primary, Gade, Meethila, additional, Yang, Edward, additional, Koh, Hyun Yong, additional, Walley, Nicole M., additional, Buckley, Anne F., additional, Sands, Tristan T., additional, Akman, Cigdem I., additional, Mikati, Mohamad A., additional, McKhann, Guy M., additional, Goldman, James E., additional, Canoll, Peter D., additional, Alexander, Allyson L., additional, Park, Kristen L., additional, Allmen, Gretchen K. Von, additional, Bhattacharjee, Meenakshi B., additional, Lidov, Hart G.W., additional, Vogel, Hannes, additional, Grant, Gerald A., additional, Porter, Brenda E., additional, Poduri, Annapurna H., additional, Crino, Peter B., additional, and Heinzen, Erin L., additional

Published
2021
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48. The benefit of diagnostic whole genome sequencing in schizophrenia and other psychotic disorders

Author

Alkelai, Anna, primary, Greenbaum, Lior, additional, Docherty, Anna R., additional, Shabalin, Andrey A., additional, Povysil, Gundula, additional, Malakar, Ayan, additional, Hughes, Daniel, additional, Delaney, Shannon L., additional, Peabody, Emma P., additional, McNamara, James, additional, Gelfman, Sahar, additional, Baugh, Evan H., additional, Zoghbi, Anthony W., additional, Harms, Matthew B., additional, Hwang, Hann-Shyan, additional, Grossman-Jonish, Anat, additional, Aggarwal, Vimla, additional, Heinzen, Erin L., additional, Jobanputra, Vaidehi, additional, Pulver, Ann E., additional, Lerer, Bernard, additional, and Goldstein, David B., additional

Published
2021
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49. Sub-genic intolerance, ClinVar, and the epilepsies: A whole-exome sequencing study of 29,165 individuals

Author

Motelow, Joshua E., primary, Povysil, Gundula, additional, Dhindsa, Ryan S., additional, Stanley, Kate E., additional, Allen, Andrew S., additional, Feng, Yen-Chen Anne, additional, Howrigan, Daniel P., additional, Abbott, Liam E., additional, Tashman, Katherine, additional, Cerrato, Felecia, additional, Cusick, Caroline, additional, Singh, Tarjinder, additional, Heyne, Henrike, additional, Byrnes, Andrea E., additional, Churchhouse, Claire, additional, Watts, Nick, additional, Solomonson, Matthew, additional, Lal, Dennis, additional, Gupta, Namrata, additional, Neale, Benjamin M., additional, Cavalleri, Gianpiero L., additional, Cossette, Patrick, additional, Cotsapas, Chris, additional, De Jonghe, Peter, additional, Dixon-Salazar, Tracy, additional, Guerrini, Renzo, additional, Hakonarson, Hakon, additional, Heinzen, Erin L., additional, Helbig, Ingo, additional, Kwan, Patrick, additional, Marson, Anthony G., additional, Petrovski, Slavé, additional, Kamalakaran, Sitharthan, additional, Sisodiya, Sanjay M., additional, Stewart, Randy, additional, Weckhuysen, Sarah, additional, Depondt, Chantal, additional, Dlugos, Dennis J., additional, Scheffer, Ingrid E., additional, Striano, Pasquale, additional, Freyer, Catharine, additional, Krause, Roland, additional, May, Patrick, additional, McKenna, Kevin, additional, Regan, Brigid M., additional, Bennett, Caitlin A., additional, Leu, Costin, additional, Leech, Stephanie L., additional, O’Brien, Terence J., additional, Todaro, Marian, additional, Stamberger, Hannah, additional, Andrade, Danielle M., additional, Ali, Quratulain Zulfiqar, additional, Sadoway, Tara R., additional, Krestel, Heinz, additional, Schaller, André, additional, Papacostas, Savvas S., additional, Kousiappa, Ioanna, additional, Tanteles, George A., additional, Christou, Yiolanda, additional, Štěrbová, Katalin, additional, Vlčková, Markéta, additional, Sedláčková, Lucie, additional, Laššuthová, Petra, additional, Klein, Karl Martin, additional, Rosenow, Felix, additional, Reif, Philipp S., additional, Knake, Susanne, additional, Neubauer, Bernd A., additional, Zimprich, Friedrich, additional, Feucht, Martha, additional, Reinthaler, Eva M., additional, Kunz, Wolfram S., additional, Zsurka, Gábor, additional, Surges, Rainer, additional, Baumgartner, Tobias, additional, von Wrede, Randi, additional, Pendziwiat, Manuela, additional, Muhle, Hiltrud, additional, Rademacher, Annika, additional, van Baalen, Andreas, additional, von Spiczak, Sarah, additional, Stephani, Ulrich, additional, Afawi, Zaid, additional, Korczyn, Amos D., additional, Kanaan, Moien, additional, Canavati, Christina, additional, Kurlemann, Gerhard, additional, Müller-Schlüter, Karen, additional, Kluger, Gerhard, additional, Häusler, Martin, additional, Blatt, Ilan, additional, Lemke, Johannes R., additional, Krey, Ilona, additional, Weber, Yvonne G., additional, Wolking, Stefan, additional, Becker, Felicitas, additional, Lauxmann, Stephan, additional, Boßelmann, Christian, additional, Kegele, Josua, additional, Hengsbach, Christian, additional, Rau, Sarah, additional, Steinhoff, Bernhard J., additional, Schulze-Bonhage, Andreas, additional, Borggräfe, Ingo, additional, Schankin, Christoph J., additional, Schubert-Bast, Susanne, additional, Schreiber, Herbert, additional, Mayer, Thomas, additional, Korinthenberg, Rudolf, additional, Brockmann, Knut, additional, Wolff, Markus, additional, Dennig, Dieter, additional, Madeleyn, Rene, additional, Kälviäinen, Reetta, additional, Saarela, Anni, additional, Timonen, Oskari, additional, Linnankivi, Tarja, additional, Lehesjoki, Anna-Elina, additional, Rheims, Sylvain, additional, Lesca, Gaetan, additional, Ryvlin, Philippe, additional, Maillard, Louis, additional, Valton, Luc, additional, Derambure, Philippe, additional, Bartolomei, Fabrice, additional, Hirsch, Edouard, additional, Michel, Véronique, additional, Chassoux, Francine, additional, Rees, Mark I., additional, Chung, Seo-Kyung, additional, Pickrell, William O., additional, Powell, Robert, additional, Baker, Mark D., additional, Fonferko-Shadrach, Beata, additional, Lawthom, Charlotte, additional, Anderson, Joseph, additional, Schneider, Natascha, additional, Balestrini, Simona, additional, Zagaglia, Sara, additional, Braatz, Vera, additional, Johnson, Michael R., additional, Auce, Pauls, additional, Sills, Graeme J., additional, Baum, Larry W., additional, Sham, Pak C., additional, Cherny, Stacey S., additional, Lui, Colin H.T., additional, Delanty, Norman, additional, Doherty, Colin P., additional, Shukralla, Arif, additional, El-Naggar, Hany, additional, Widdess-Walsh, Peter, additional, Barišić, Nina, additional, Canafoglia, Laura, additional, Franceschetti, Silvana, additional, Castellotti, Barbara, additional, Granata, Tiziana, additional, Ragona, Francesca, additional, Zara, Federico, additional, Iacomino, Michele, additional, Riva, Antonella, additional, Madia, Francesca, additional, Vari, Maria Stella, additional, Salpietro, Vincenzo, additional, Scala, Marcello, additional, Mancardi, Maria Margherita, additional, Nobili, Lino, additional, Amadori, Elisabetta, additional, Giacomini, Thea, additional, Bisulli, Francesca, additional, Pippucci, Tommaso, additional, Licchetta, Laura, additional, Minardi, Raffaella, additional, Tinuper, Paolo, additional, Muccioli, Lorenzo, additional, Mostacci, Barbara, additional, Gambardella, Antonio, additional, Labate, Angelo, additional, Annesi, Grazia, additional, Manna, Lorella, additional, Gagliardi, Monica, additional, Parrini, Elena, additional, Mei, Davide, additional, Vetro, Annalisa, additional, Bianchini, Claudia, additional, Montomoli, Martino, additional, Doccini, Viola, additional, Barba, Carmen, additional, Hirose, Shinichi, additional, Ishii, Atsushi, additional, Suzuki, Toshimitsu, additional, Inoue, Yushi, additional, Yamakawa, Kazuhiro, additional, Beydoun, Ahmad, additional, Nasreddine, Wassim, additional, Khoueiry Zgheib, Nathalie, additional, Tumiene, Birute, additional, Utkus, Algirdas, additional, Sadleir, Lynette G., additional, King, Chontelle, additional, Caglayan, S. Hande, additional, Arslan, Mutluay, additional, Yapıcı, Zuhal, additional, Topaloglu, Pınar, additional, Kara, Bulent, additional, Yis, Uluc, additional, Turkdogan, Dilsad, additional, Gundogdu-Eken, Aslı, additional, Bebek, Nerses, additional, Uğur-İşeri, Sibel, additional, Baykan, Betül, additional, Salman, Barış, additional, Haryanyan, Garen, additional, Yücesan, Emrah, additional, Kesim, Yeşim, additional, Özkara, Çiğdem, additional, Tsai, Meng-Han, additional, Ho, Chen-Jui, additional, Lin, Chih-Hsiang, additional, Lin, Kuang-Lin, additional, Chou, I-Jun, additional, Poduri, Annapurna, additional, Shiedley, Beth R., additional, Shain, Catherine, additional, Noebels, Jeffrey L., additional, Goldman, Alicia, additional, Busch, Robyn M., additional, Jehi, Lara, additional, Najm, Imad M., additional, Ferguson, Lisa, additional, Khoury, Jean, additional, Glauser, Tracy A., additional, Clark, Peggy O., additional, Buono, Russell J., additional, Ferraro, Thomas N., additional, Sperling, Michael R., additional, Lo, Warren, additional, Privitera, Michael, additional, French, Jacqueline A., additional, Schachter, Steven, additional, Kuzniecky, Ruben I., additional, Devinsky, Orrin, additional, Hegde, Manu, additional, Greenberg, David A., additional, Ellis, Colin A., additional, Goldberg, Ethan, additional, Helbig, Katherine L., additional, Cosico, Mahgenn, additional, Vaidiswaran, Priya, additional, Fitch, Eryn, additional, Berkovic, Samuel F., additional, Lerche, Holger, additional, Lowenstein, Daniel H., additional, and Goldstein, David B., additional

Published
2021
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50. Distinct gene-set burden patterns underlie common generalized and focal epilepsies

Author

Koko, Mahmoud, primary, Krause, Roland, additional, Sander, Thomas, additional, Bobbili, Dheeraj Reddy, additional, Nothnagel, Michael, additional, May, Patrick, additional, Lerche, Holger, additional, Feng, Yen-Chen Anne, additional, Howrigan, Daniel P, additional, Abbott, Liam E, additional, Tashman, Katherine, additional, Cerrato, Felecia, additional, Singh, Tarjinder, additional, Heyne, Henrike, additional, Byrnes, Andrea, additional, Churchhouse, Claire, additional, Watts, Nick, additional, Solomonson, Matthew, additional, Lal, Dennis, additional, Heinzen, Erin L, additional, Dhindsa, Ryan S, additional, Stanley, Kate E, additional, Cavalleri, Gianpiero L, additional, Hakonarson, Hakon, additional, Helbig, Ingo, additional, Weckhuysen, Sarah, additional, Petrovski, Slavé, additional, Kamalakaran, Sitharthan, additional, Sisodiya, Sanjay M, additional, Cossette, Patrick, additional, Cotsapas, Chris, additional, DeJonghe, Peter, additional, Dixon-Salazar, Tracy, additional, Guerrini, Renzo, additional, Kwan, Patrick, additional, Marson, Anthony G, additional, Stewart, Randy, additional, Depondt, Chantal, additional, Dlugos, Dennis J, additional, Scheffer, Ingrid E, additional, Striano, Pasquale, additional, Freyer, Catharine, additional, McKenna, Kevin, additional, Regan, Brigid M, additional, Bellows, Susannah T, additional, Leu, Costin, additional, Bennett, Caitlin A, additional, Johns, Esther M C, additional, Macdonald, Alexandra, additional, Shilling, Hannah, additional, Burgess, Rosemary, additional, Weckhuysen, Dorien, additional, Bahlo, Melanie, additional, O'Brien, Terence J, additional, Todaro, Marian, additional, Stamberger, Hannah, additional, Andrade, Danielle M, additional, Sadoway, Tara R, additional, Mo, Kelly, additional, Krestel, Heinz, additional, Gallati, Sabina, additional, Papacostas, Savvas S, additional, Kousiappa, Ioanna, additional, Tanteles, George A, additional, Štěrbová, Katalin, additional, Vlčková, Markéta, additional, Sedláčková, Lucie, additional, Laššuthová, Petra, additional, Klein, Karl Martin, additional, Rosenow, Felix, additional, Reif, Philipp S, additional, Knake, Susanne, additional, Kunz, Wolfram S, additional, Zsurka, Gábor, additional, Elger, Christian E, additional, Bauer, Jürgen, additional, Rademacher, Michael, additional, Pendziwiat, Manuela, additional, Muhle, Hiltrud, additional, Rademacher, Annika, additional, vanBaalen, Andreas, additional, vonSpiczak, Sarah, additional, Stephani, Ulrich, additional, Afawi, Zaid, additional, Korczyn, Amos D, additional, Kanaan, Moien, additional, Canavati, Christina, additional, Kurlemann, Gerhard, additional, Müller-Schlüter, Karen, additional, Kluger, Gerhard, additional, Häusler, Martin, additional, Blatt, Ilan, additional, Lemke, Johannes R, additional, Krey, Ilona, additional, Weber, Yvonne G, additional, Wolking, Stefan, additional, Becker, Felicitas, additional, Hengsbach, Christian, additional, Rau, Sarah, additional, Maisch, Ana F, additional, Steinhoff, Bernhard J, additional, Schulze-Bonhage, Andreas, additional, Schubert-Bast, Susanne, additional, Schreiber, Herbert, additional, Borggräfe, Ingo, additional, Schankin, Christoph J, additional, Mayer, Thomas, additional, Korinthenberg, Rudolf, additional, Brockmann, Knut, additional, Dennig, Dieter, additional, Madeleyn, Rene, additional, Kälviäinen, Reetta, additional, Auvinen, Pia, additional, Saarela, Anni, additional, Linnankivi, Tarja, additional, Lehesjoki, Anna-Elina, additional, Rees, Mark I, additional, Chung, Seo-Kyung, additional, Pickrell, William O, additional, Powell, Robert, additional, Schneider, Natascha, additional, Balestrini, Simona, additional, Zagaglia, Sara, additional, Braatz, Vera, additional, Johnson, Michael R, additional, Auce, Pauls, additional, Sills, Graeme J, additional, Baum, Larry W, additional, Sham, Pak C, additional, Cherny, Stacey S, additional, Lui, Colin H T, additional, Barišić, Nina, additional, Delanty, Norman, additional, Doherty, Colin P, additional, Shukralla, Arif, additional, McCormack, Mark, additional, El-Naggar, Hany, additional, Canafoglia, Laura, additional, Franceschetti, Silvana, additional, Castellotti, Barbara, additional, Granata, Tiziana, additional, Zara, Federico, additional, Iacomino, Michele, additional, Madia, Francesca, additional, Vari, Maria Stella, additional, Mancardi, Maria Margherita, additional, Salpietro, Vincenzo, additional, Bisulli, Francesca, additional, Tinuper, Paolo, additional, Licchetta, Laura, additional, Pippucci, Tommaso, additional, Stipa, Carlotta, additional, Minardi, Raffaella, additional, Gambardella, Antonio, additional, Labate, Angelo, additional, Annesi, Grazia, additional, Manna, Lorella, additional, Gagliardi, Monica, additional, Parrini, Elena, additional, Mei, Davide, additional, Vetro, Annalisa, additional, Bianchini, Claudia, additional, Montomoli, Martino, additional, Doccini, Viola, additional, Marini, Carla, additional, Suzuki, Toshimitsu, additional, Inoue, Yushi, additional, Yamakawa, Kazuhiro, additional, Tumiene, Birute, additional, Sadleir, Lynette G, additional, King, Chontelle, additional, Mountier, Emily, additional, Caglayan, Hande S, additional, Arslan, Mutluay, additional, Yapıcı, Zuhal, additional, Yis, Uluc, additional, Topaloglu, Pınar, additional, Kara, Bulent, additional, Turkdogan, Dilsad, additional, Gundogdu-Eken, Aslı, additional, Bebek, Nerses, additional, Uğur-İşeri, Sibel, additional, Baykan, Betül, additional, Salman, Barış, additional, Haryanyan, Garen, additional, Yücesan, Emrah, additional, Kesim, Yeşim, additional, Özkara, Çiğdem, additional, Poduri, Annapurna, additional, Shiedley, Beth R, additional, Shain, Catherine, additional, Buono, Russell J, additional, Ferraro, Thomas N, additional, Sperling, Michael R, additional, Lo, Warren, additional, Privitera, Michael, additional, French, Jacqueline A, additional, Schachter, Steven, additional, Kuzniecky, Ruben I, additional, Devinsky, Orrin, additional, Hegde, Manu, additional, Khankhanian, Pouya, additional, Helbig, Katherine L, additional, Ellis, Colin A, additional, Spalletta, Gianfranco, additional, Piras, Fabrizio, additional, Piras, Federica, additional, Gili, Tommaso, additional, Ciullo, Valentina, additional, Reif, Andreas, additional, McQuillin, Andrew, additional, Bass, Nick, additional, McIntosh, Andrew, additional, Blackwood, Douglas, additional, Johnstone, Mandy, additional, Palotie, Aarno, additional, Pato, Michele T, additional, Pato, Carlos N, additional, Bromet, Evelyn J, additional, Carvalho, Celia Barreto, additional, Achtyes, Eric D, additional, Azevedo, Maria Helena, additional, Kotov, Roman, additional, Lehrer, Douglas S, additional, Malaspina, Dolores, additional, Marder, Stephen R, additional, Medeiros, Helena, additional, Morley, Christopher P, additional, Perkins, Diana O, additional, Sobell, Janet L, additional, Buckley, Peter F, additional, Macciardi, Fabio, additional, Rapaport, Mark H, additional, Knowles, James A, additional, Cohort, Genomic Psychiatry, additional, Fanous, Ayman H, additional, McCarroll, Steven A, additional, Gupta, Namrata, additional, Gabriel, Stacey B, additional, Daly, Mark J, additional, Lander, Eric S, additional, Lowenstein, Daniel H, additional, Goldstein, David B, additional, Berkovic, Samuel F, additional, and Neale, Benjamin M, additional

Published
2021
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