Search

Your search keyword '"Gruber-Sedlmayr, U"' showing total 7 results
Start Over Author "Gruber-Sedlmayr, U" Topic epilepsy
7 results on '"Gruber-Sedlmayr, U"'

1. Variants in the degron of AFF3 are associated with intellectual disability, mesomelic dysplasia, horseshoe kidney, and epileptic encephalopathy.

Author

Voisin N, Schnur RE, Douzgou S, Hiatt SM, Rustad CF, Brown NJ, Earl DL, Keren B, Levchenko O, Geuer S, Verheyen S, Johnson D, Zarate YA, Hančárová M, Amor DJ, Bebin EM, Blatterer J, Brusco A, Cappuccio G, Charrow J, Chatron N, Cooper GM, Courtin T, Dadali E, Delafontaine J, Del Giudice E, Doco M, Douglas G, Eisenkölbl A, Funari T, Giannuzzi G, Gruber-Sedlmayr U, Guex N, Heron D, Holla ØL, Hurst ACE, Juusola J, Kronn D, Lavrov A, Lee C, Lorrain S, Merckoll E, Mikhaleva A, Norman J, Pradervand S, Prchalová D, Rhodes L, Sanders VR, Sedláček Z, Seebacher HA, Sellars EA, Sirchia F, Takenouchi T, Tanaka AJ, Taska-Tench H, Tønne E, Tveten K, Vitiello G, Vlčková M, Uehara T, Nava C, Yalcin B, Kosaki K, Donnai D, Mundlos S, Brunetti-Pierri N, Chung WK, and Reymond A

Subjects
Adolescent, Amino Acid Sequence, Animals, Brain Diseases etiology, Child, Child, Preschool, Epilepsy complications, Evolution, Molecular, Female, Gene Frequency, Humans, Infant, Male, Mice, Models, Molecular, Nuclear Proteins chemistry, Nuclear Proteins deficiency, Phenotype, Protein Stability, Syndrome, Transcriptional Elongation Factors chemistry, Transcriptional Elongation Factors genetics, Young Adult, Zebrafish genetics, Brain Diseases genetics, Epilepsy genetics, Fused Kidney genetics, Intellectual Disability genetics, Mutation, Missense, Nuclear Proteins genetics, Osteochondrodysplasias genetics
Abstract

The ALF transcription factor paralogs, AFF1, AFF2, AFF3, and AFF4, are components of the transcriptional super elongation complex that regulates expression of genes involved in neurogenesis and development. We describe an autosomal dominant disorder associated with de novo missense variants in the degron of AFF3, a nine amino acid sequence important for its binding to ubiquitin ligase, or with de novo deletions of this region. The sixteen affected individuals we identified, along with two previously reported individuals, present with a recognizable pattern of anomalies, which we named KINSSHIP syndrome (KI for horseshoe kidney, NS for Nievergelt/Savarirayan type of mesomelic dysplasia, S for seizures, H for hypertrichosis, I for intellectual disability, and P for pulmonary involvement), partially overlapping the AFF4-associated CHOPS syndrome. Whereas homozygous Aff3 knockout mice display skeletal anomalies, kidney defects, brain malformations, and neurological anomalies, knockin animals modeling one of the microdeletions and the most common of the missense variants identified in affected individuals presented with lower mesomelic limb deformities like KINSSHIP-affected individuals and early lethality, respectively. Overexpression of AFF3 in zebrafish resulted in body axis anomalies, providing some support for the pathological effect of increased amount of AFF3. The only partial phenotypic overlap of AFF3- and AFF4-associated syndromes and the previously published transcriptome analyses of ALF transcription factors suggest that these factors are not redundant and each contributes uniquely to proper development., (Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Published
2021
Full Text
View/download PDF

2. Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.

Author

Lal D, Reinthaler EM, Dejanovic B, May P, Thiele H, Lehesjoki AE, Schwarz G, Riesch E, Ikram MA, van Duijn CM, Uitterlinden AG, Hofman A, Steinböck H, Gruber-Sedlmayr U, Neophytou B, Zara F, Hahn A, Gormley P, Becker F, Weber YG, Cilio MR, Kunz WS, Krause R, Zimprich F, Lemke JR, Nürnberg P, Sander T, Lerche H, and Neubauer BA

Subjects
Amino Acid Substitution, Case-Control Studies, Epilepsy epidemiology, Female, Humans, Male, Risk Factors, Syndrome, Epilepsy genetics, Mutation, Missense, NAV1.1 Voltage-Gated Sodium Channel genetics
Abstract

Objective: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic., Methods: We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients., Results and Interpretation: We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10-4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions.

Published
2016
Full Text
View/download PDF

3. Left ventricular hypertrabeculation/noncompaction with epilepsy, other heart defects, minor facial anomalies and new copy number variants.

Author

Nagel B, Gruber-Sedlmayr U, Uhrig S, Stöllberger C, Klopocki E, and Finsterer J

Subjects
Aortic Valve Stenosis genetics, Child, Preschool, DNA Copy Number Variations, Epilepsy genetics, Female, Humans, Isolated Noncompaction of the Ventricular Myocardium genetics, Oligonucleotide Array Sequence Analysis, Pulmonary Valve Stenosis genetics, Aortic Valve Stenosis diagnosis, Epilepsy diagnosis, Face abnormalities, Isolated Noncompaction of the Ventricular Myocardium diagnosis, Pulmonary Valve Stenosis diagnosis
Abstract

Background: Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown etiology which has been described in children as well as in adults with and without chromosomal aberrations. LVHT has been reported in association with various cardiac and extracardiac abnormalities like epilepsy and facial dysmorphism., Case Presentation: A unique combination of LVHT, atrial septal defect, pulmonary valve stenosis, aortic stenosis, epilepsy and minor facial anomalies is presented in a 5.5 years old girl. Microarray-based genomic hybridization (array-CGH) detected six previously not described copy number variants (CNVs) inherited from a clinically unaffected father and minimally affected mother, thus, most likely, not clinically significant but rare benign variants., Conclusions: Despite this complex phenotype de novo microdeletions or microduplications were not detected by array CGH. Further investigations, such as whole exome sequencing, could reveal point mutations and small indels as the possible cause.

Published
2012
Full Text
View/download PDF

4. Epilepsy in tuberous sclerosis complex: Findings from the TOSCA Study

Author

Nabbout, R, Belousova, E, Benedik, Mp, Carter, T, Cottin, V, Curatolo, P, Dahlin, M, Damato, L, D'Augeres, Gb, de Vries, Pj, Ferreira, Jc, Feucht, M, Fladrowski, C, Hertzberg, C, Jozwiak, S, Lawson, Ja, Macaya, A, Marques, R, O'Callaghan, F, Qin, J, Sander, V, Sauter, M, Shah, S, Takahashi, Y, Touraine, R, Youroukos, S, Zonnenberg, B, Jansen, A, Kingswood, Jc, Shinohara, N, Horie, S, Kubota, M, Tohyama, J, Imai, K, Kaneda, M, Kaneko, H, Uchida, Y, Endo, S, Inoue, Y, Uruno, K, Serdaroglu, A, Yapici, Z, Anlar, B, Altunbasak, S, Lvova, O, Valeryevich Belyaev, O, Agranovich, O, Vladislavovna Levitina, E, Vladimirovna Maksimova, Y, Karas, A, Jiang, Y, Zou, L, Xu, K, Zhang, Y, Luan, G, Wang, Y, Jin, M, Ye, D, Liao, W, Zhou, L, Liu, J, Liao, J, Yan, B, Deng, Y, Jiang, L, Liu, Z, Huang, S, Li, H, Kim, K, Chen, P, Lee, H, Tsai, J, Chi, C, Huang, C, Riney, K, Yates, D, Kwan, P, Likasitwattanakul, S, Nabangchang, C, Thampratankul Krisnachai Chomtho, L, Katanyuwong, K, Sriudomkajorn, S, Wilmshurst, J, Segel, R, Gilboa, T, Tzadok, M, Fattal-Valevski, A, Papathanasopoulos, P, Syrigou Papavasiliou, A, Giannakodimos, S, Gatzonis, S, Pavlou, E, Tzoufi, M, Dhooghe, M, Verhelst, H, Roelens, F, Cecile Nassogne, M, Defresne, P, De Waele, L, Leroy, P, Demonceau, N, Van Bogaert, P, Ceulemans, B, Dom, L, Castelnau, P, De Saint Martin, A, Riquet, A, Milh, M, Cances, C, Pedespan, J, Ville, D, Roubertie, A, Auvin, S, Berquin, P, Richelme, C, Allaire, C, Gueden, S, Nguyen The Tich, S, Godet, B, Rojas, Mlrf, Planas, Jc, Bermejo, Am, Dura, Ps, Aparicio, Sr, Gonzalez, Mjm, Pison, Jl, Blanco Barca, Mo, Laso, El, Luengo, Oa, Rodriguez, Fja, Dieguez, Im, Salas, Ac, Carrera, Im, Salcedo, Em, Petri, Mey, Candela, Rc, Carrilho, Idc, Vieira, Jp, Monteiro, Jpdso, Leao, Mjsdof, Luis, Csmr, Pires Mendonca, C, Endziniene, M, Strautmanis, J, Talvik, I, Canevini, Mp, Gambardella, A, Pruna, D, Buono, S, Fontana, E, Bernardina, Bd, Burloiu, C, Cosma, Isb, Vintan, Ma, Popescu, L, Zitterbart, K, Payerova, J, Bratsky, L, Zilinska, Z, Gruber-Sedlmayr, U, Haberlandt, E, Rostasy, K, Pataraia, E, Elmslie, F, Ann Johnston, C, Crawford, P, Uldall, P, Uvebrant, P, Rask, O, Bjoernvold, M, Sloerdahl, A, Solhoff, R, Jaatun, Msg, Mandera, M, Radzikowska, Ej, Wysocki, M, Fischereder, M, Kurlemann, G, Wilken, B, Wiemer-Kruel, A, Budde, K, Marquard, K, Knuf, M, Hahn, A, Hartmann, H, Merkenschlager, A, and Trollmann, R

Subjects
0301 basic medicine, medicine.medical_specialty, Pediatrics, Neurology, Disease, tuberous sclerosis complex, 030105 genetics & heredity, registry, 03 medical and health sciences, Tuberous sclerosis, Epilepsy, 0302 clinical medicine, Intellectual disability, medicine, Seizure control, TOSCA, business.industry, epilepsy, medicine.disease, Settore MED/39 - Neuropsichiatria Infantile, 3. Good health, medicine.anatomical_structure, Cohort, Full‐length Original Research, Neurology (clinical), TSC1, business, 030217 neurology & neurosurgery
Abstract

Summary Objective To present the baseline data of the international TuberOus SClerosis registry to increase disease Awareness (TOSCA) with emphasis on the characteristics of epilepsies associated with tuberous sclerosis complex (TSC). Methods Retrospective and prospective patients’ data on all aspects of TSC were collected from multiple countries worldwide. Epilepsy variables included seizure type, age at onset, type of treatment, and treatment outcomes and association with genotype, seizures control, and intellectual disability. As for noninterventional registries, the study protocol did not specify any particular clinical instruments, laboratory investigations, or intervention. Evaluations included those required for diagnosis and management following local best practice. Results Epilepsy was reported in 83.6% of patients (1852/2216) at baseline; 38.9% presented with infantile spasms and 67.5% with focal seizures. The mean age at diagnosis of infantile spasms was 0.4 year (median

Published
2019

5. Epileptic phenotypes, electroclinical features and clinical characteristics in 17 children with anti-NMDAR encephalitis.

Author

Haberlandt, E., Ensslen, M., Gruber-Sedlmayr, U., Plecko, B., Brunner-Krainz, M., Schimmel, M., Schubert-Bast, S., Neirich, U., Philippi, H., Kurleman, G., Tardieu, M., Wohlrab, G., Borggraefe, I., and Rostásy, K.

Abstract

Background Anti-N-methyl d -aspartate receptor (NMDAR) encephalitis is a rare disorder characterized by seizures, neuropsychiatric symptoms, dyskinesia and autonomic instability. Objective Aim of the present study was to evaluate the seizure phenotypes and electroencephalogram (EEG) features in children with anti-NMDAR encephalitis. Methods Seizure types, electroclinical features and clinical characteristics of 17 children with anti-NMDAR encephalitis were analysed in a retrospective case series from nine centres in Europe. Results Nearly half (8/17) of the children presented with psychiatric symptoms, whereas in 4/17 patients seizures were the first symptom and in 5/17 both symptoms occurred at the same time. During the following course seizures were reported in 16/17 children. The first EEG detected generalized slowing in 11/17 patients, focal slowing in 3/17 and normal background activity in only 3/17 children. The extreme delta brush (EDB) pattern was detected in 9/17 (53%) patients. Conclusion In addition to psychiatric symptoms, children with anti-NMDAR encephalitis often show generalized slowing in EEG with or without seizures at initial presentation. EDB is present in half of all children and is potentially a helpful tool for early detection of this immune-mediated disease. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

6. Variants in the degron of AFF3 are associated with intellectual disability, mesomelic dysplasia, horseshoe kidney, and epileptic encephalopathy

Author

Rhonda E. Schnur, Fabio Sirchia, Olga Levchenko, Caroline Nava, Jane Juusola, Sarah Verheyen, Marketa Vlckova, Lindsay Rhodes, Gregory M. Cooper, Darina Prchalova, Thomas Courtin, Øystein L. Holla, David Kronn, Akemi J. Tanaka, E. Martina Bebin, Tara Funari, Miroslava Hancarova, Ennio Del Giudice, Nicolas Guex, Astrid Eisenkölbl, Dawn L. Earl, Toshiki Takenouchi, Ursula Gruber-Sedlmayr, Sedlácek Z, Sofia Douzgou, Heidelis A. Seebacher, Gerarda Cappuccio, Jasmin Blatterer, Anna Mikhaleva, Dian Donnai, Wendy K. Chung, Else Merckoll, Natasha J Brown, Elizabeth A. Sellars, Stefan Mundlos, Susan M. Hiatt, Giuliana Giannuzzi, Sinje Geuer, Giuseppina Vitiello, Séverine Lorrain, Alexandre Reymond, David J. Amor, Nicolas Chatron, Julien Delafontaine, Martine Doco, Kristian Tveten, Cecilie F. Rustad, Sylvain Pradervand, Delphine Héron, Alfredo Brusco, Elena L. Dadali, Nicola Brunetti-Pierri, Boris Keren, Yuri A. Zarate, Crystle Lee, Joel Charrow, Binnaz Yalcin, Heidi Taska-Tench, Elin Tønne, Tomoko Uehara, Alexander Lavrov, Jennifer Norman, Norine Voisin, Anna C.E. Hurst, Victoria R. Sanders, Ganka Douglas, Diana Johnson, Kenjiro Kosaki, Université de Lausanne = University of Lausanne (UNIL), Cooper Medical School of Rowan University [Camden] (CMSRU), Manchester University NHS Foundation Trust (MFT), University of Manchester [Manchester], HudsonAlpha Institute for Biotechnology [Huntsville, AL], Oslo University Hospital [Oslo], Victorian Clinical Genetics Services [Melbourne, VIC, Australia] (VCGS), Murdoch Children's Research Institute (MCRI), University of Melbourne, Seattle Children’s Hospital, Groupe de Recherche Clinique : Déficience Intellectuelle et Autisme [ CHU Pitié-Salpêtrière AP-HP] (GRC : DIA), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Research Centre for Medical Genetics [Moscow, Russia] (RCMG), Max Planck Institute for Molecular Genetics (MPIMG), Max-Planck-Gesellschaft, Medical University of Graz, Sheffield Children's NHS Foundation Trust, University of Arkansas at Little Rock, Charles University [Prague] (CU), University Hospital Motol [Prague], University of Alabama at Birmingham [ Birmingham] (UAB), Università degli studi di Torino = University of Turin (UNITO), Azienda Ospedalerio - Universitaria Città della Salute e della Scienza di Torino = University Hospital Città della Salute e della Scienza di Torino, University of Naples Federico II = Università degli studi di Napoli Federico II, Ann & Robert H. Lurie Children's Hospital of Chicago, Swiss Institute of Bioinformatics [Lausanne] (SIB), Hémostase et Remodelage Vasculaire Post-Ischémie (HERVI - EA 3801), Université de Reims Champagne-Ardenne (URCA), GeneDx [Gaithersburg, MD, USA], Johannes Kepler University Linz [Linz] (JKU), Telemark Hospital Trust [Skien, Norway], New York Medical College (NYMC), Integris Pediatric Neurology [Oklahoma City, OK, USA] (IPN), Institute for Maternal and Child Health - IRCCS 'Burlo Garofolo' [Trieste], Keio University School of Medicine [Tokyo, Japan], Columbia University [New York], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Manchester Centre for Genomic Medicine [Manchester, UK] (MCGM), St Mary's Hospital Manchester-Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester]-University of Manchester [Manchester]-Manchester University NHS Foundation Trust (MFT)-Faculty of Biology, Medicine and Health [Manchester, UK], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Dupuis, Christine, Voisin, N., Schnur, R. E., Douzgou, S., Hiatt, S. M., Rustad, C. F., Brown, N. J., Earl, D. L., Keren, B., Levchenko, O., Geuer, S., Verheyen, S., Johnson, D., Zarate, Y. A., Hancarova, M., Amor, D. J., Bebin, E. M., Blatterer, J., Brusco, A., Cappuccio, G., Charrow, J., Chatron, N., Cooper, G. M., Courtin, T., Dadali, E., Delafontaine, J., Del Giudice, E., Doco, M., Douglas, G., Eisenkolbl, A., Funari, T., Giannuzzi, G., Gruber-Sedlmayr, U., Guex, N., Heron, D., Holla, O. L., Hurst, A. C. E., Juusola, J., Kronn, D., Lavrov, A., Lee, C., Lorrain, S., Merckoll, E., Mikhaleva, A., Norman, J., Pradervand, S., Prchalova, D., Rhodes, L., Sanders, V. R., Sedlacek, Z., Seebacher, H. A., Sellars, E. A., Sirchia, F., Takenouchi, T., Tanaka, A. J., Taska-Tench, H., Tonne, E., Tveten, K., Vitiello, G., Vlckova, M., Uehara, T., Nava, C., Yalcin, B., Kosaki, K., Donnai, D., Mundlos, S., Brunetti Pierri, N., Chung, W. K., and Reymond, A.

Subjects
Male, Models, Molecular, Hypertrichosis, [SDV]Life Sciences [q-bio], Mesomelic Dysplasia, Transcriptome, Mice, Gene Frequency, Missense mutation, Child, Zebrafish, Genetics (clinical), Genetics, Brain Diseases, 0303 health sciences, biology, Protein Stability, 030305 genetics & heredity, AFF3, AFF4, horseshoe kidney, intellectual disability, mesomelic dysplasia, Nuclear Proteins, Syndrome, Phenotype, Ubiquitin ligase, [SDV] Life Sciences [q-bio], Child, Preschool, Female, Transcriptional Elongation Factors, Adolescent, Mutation, Missense, Osteochondrodysplasias, Article, Evolution, Molecular, Young Adult, 03 medical and health sciences, medicine, Animals, Humans, Amino Acid Sequence, Fused Kidney, 030304 developmental biology, Epilepsy, Infant, Horseshoe kidney, biology.organism_classification, medicine.disease, biology.protein
Abstract

International audience; The ALF transcription factor paralogs, AFF1, AFF2, AFF3, and AFF4, are components of the transcriptional super elongation complex that regulates expression of genes involved in neurogenesis and development. We describe an autosomal dominant disorder associated with de novo missense variants in the degron of AFF3, a nine amino acid sequence important for its binding to ubiquitin ligase, or with de novo deletions of this region. The sixteen affected individuals we identified, along with two previously reported individuals, present with a recognizable pattern of anomalies, which we named KINSSHIP syndrome (KI for horseshoe kidney, NS for Nievergelt/Savarirayan type of mesomelic dysplasia, S for seizures, H for hypertrichosis, I for intellectual disability, and P for pulmonary involvement), partially overlapping the AFF4-associated CHOPS syndrome. Whereas homozygous Aff3 knockout mice display skeletal anomalies, kidney defects, brain malformations, and neurological anomalies, knockin animals modeling one of the microdeletions and the most common of the missense variants identified in affected individuals presented with lower mesomelic limb deformities like KINSSHIP-affected individuals and early lethality, respectively. Overexpression of AFF3 in zebrafish resulted in body axis anomalies, providing some support for the pathological effect of increased amount of AFF3. The only partial phenotypic overlap of AFF3-and AFF4-associated syndromes and the previously published transcriptome analyses of ALF transcription factors suggest that these factors are not redundant and each contributes uniquely to proper development.

Published
2021
Full Text
View/download PDF

7. 16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy

Author

Eva M. Reinthaler, Dennis Lal, Sebastien Lebon, Michael S. Hildebrand, Hans-Henrik M. Dahl, Brigid M. Regan, Martha Feucht, Hannelore Steinböck, 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, Susanne Schoch, Albert J. Becker, Andreas Hahn, Katrin Männik, Mohammad R. Toliat, Georg Winterer, Holger Lerche, Peter Nürnberg, Heather Mefford, Ingrid E. Scheffer, Samuel F. Berkovic, Jacques S. Beckmann, Thomas Sander, Sebastien Jacquemont, Alexandre Reymond, Fritz Zimprich, Bernd A. Neubauer, Bernd Neubauer, Martina Mörzinger, Arvid Suls, Sarah Weckhuysen, Lieve Claes, Liesbet Deprez, Katrien Smets, Tine Van Dyck, Tine Deconinck, Peter De Jonghe, Rikke S Møller, Laura L. Klitten, Helle Hjalgrim, Kiel Campus, Ingo Helbig, Hiltrud Muhle, Philipp Ostertag, Sarah von Spiczak, Ulrich Stephani, Holger Trucks, Christian E. Elger, Ailing A. Kleefuß-Lie, Wolfram S. Kunz, Rainer Surges, Verena Gaus, Dieter Janz, Bettina Schmitz, Felix Rosenow, Karl Martin Klein, Philipp S. Reif, Wolfgang H. Oertel, Hajo M. Hamer, Felicitas Becker, Yvonne Weber, Bobby P.C. Koeleman, Carolien de Kovel, Dick Lindhout, Agnès Ameil, Joris Andrieux, Sonia Bouquillon, Odile Boute, Jeanne de Flandre, Jean Marie Cuisset, Jean-Christophe Cuvellier, Roger Salengro, Albert David, Bert de Vries, Marie-Ange Delrue, Martine Doco-Fenzy, Bridget A. Fernandez, Delphine Heron, Boris Keren, Robert Lebel, Bruno Leheup, Suzanne Lewis, Maria Antonietta Mencarelli, Cyril Mignot, Jean-Claude Minet, Alexandre Moerman, Fanny Morice-Picard, Mafalda Mucciolo, Katrin Ounap, Laurent Pasquier, Florence Petit, Francesca Ragona, Evica Rajcan-Separovic, Alessandra Renieri, Claudine Rieubland, Damien Sanlaville, Elisabeth Sarrazin, Yiping Shen, Mieke van Haelst, Anneke Vulto-van Silfhout, 16p11.2 European Consortium, EPICURE Consortium, EuroEPINOMICS Consortium, Reinthaler, EM., Zimprich, F., Feucht, M., Steinböck, H., Neophytou, B., Geldner, J., Gruber-Sedlmayr, U., Haberlandt, E., Ronen, GM., Roche, L., Lal, D., Nürnberg, P., Sander, T., Lerche, H., Neubauer, B., Mörzinger, M., Suls, A., Weckhuysen, S., Claes, L., Deprez, L., Smets, K., Van Dyck, T., Deconinck, T., De Jonghe, P., Møller, RS., Klitten, LL., Hjalgrim, H., Campus, K., Helbig, I., Muhle, H., Ostertag, P., von Spiczak, S., Stephani, U., Trucks, H., Elger, CE., Kleefuß-Lie, AA., Kunz, WS., Surges, R., Gaus, V., Janz, D., Schmitz, B., Rosenow, F., Klein, KM., Reif, PS., Oertel, WH., Hamer, HM., Becker, F., Weber, Y., Koeleman, BP., de Kovel, C., Lindhout, D., Ameil, A., Andrieux, J., Bouquillon, S., Boute, O., Cordier, MP., Cuisset, JM., Cuvellier, JC., David, A., de Vries, B., Delrue, MA., Doco-Fenzy, M., Fernandez, BA., Heron, D., Keren, B., Lebel, R., Leheup, B., Lewis, S., Mencarelli, MA., Mignot, C., Minet, JC., Moerman, A., Morice-Picard, F., Mucciolo, M., Ounap, K., Pasquier, L., Petit, F., Ragona, F., Rajcan-Separovic, E., Renieri, A., Rieubland, C., Sanlaville, D., Sarrazin, E., Shen, Y., van Haelst, M., Vulto-van Silfhout, A., and Other departments

Subjects
Male, DNA Copy Number Variations, Chromosomes, Human, Pair 22, 610 Medicine & health, Locus (genetics), Biology, Polymorphism, Single Nucleotide, Temporal lobe, Epilepsy, Gene duplication, Chromosome Duplication, Genetics, medicine, Humans, Copy-number variation, Child, Molecular Biology, Genetics (clinical), Chromosomes, Human, Pair 15, Infant, General Medicine, Odds ratio, medicine.disease, Epilepsy, Rolandic, Rolandic epilepsy, Exact test, Chromosomes, Human, Pair 1, Child, Preschool, Female, Chromosomes, Human, Pair 16
Abstract

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65,046 European population controls (5/393 cases versus 32/65,046 controls; Fisher's exact test P = 2.83 × 10(-6), odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10(-4)). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical RE.

Published
2014
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results