Journal ArticleDOI
Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes
Johannes R. Lemke,Dennis Lal,Eva M. Reinthaler,Isabelle Steiner,Michael Nothnagel,Michael Alber,Kirsten Geider,Bodo Laube,Michael Schwake,Katrin Finsterwalder,Andre Franke,Markus Schilhabel,Johanna A. Jähn,Hiltrud Muhle,Rainer Boor,Wim Van Paesschen,Roberto Caraballo,Natalio Fejerman,Sarah Weckhuysen,Peter De Jonghe,Jan Larsen,Rikke S. Møller,Helle Hjalgrim,Laura Addis,Shan Tang,Elaine Hughes,Deb K. Pal,Kadi Veri,Ulvi Vaher,Tiina Talvik,Petia Dimova,Rosa Guerrero López,José M. Serratosa,Tarja Linnankivi,Anna-Elina Lehesjoki,Susanne Ruf,Markus Wolff,Sarah E. Buerki,Gabriele Wohlrab,Judith Kroell,Alexandre N. Datta,Barbara Fiedler,Gerhard Kurlemann,Gerhard Kluger,Andreas Hahn,D Edda Haberlandt,Christina Kutzer,Jürgen Sperner,Felicitas Becker,Yvonne G. Weber,Martha Feucht,Hannelore Steinböck,Birgit Neophythou,Gabriel M. Ronen,Ursula Gruber-Sedlmayr,Julia Geldner,Robert J. Harvey,Per Hoffmann,Per Hoffmann,Stefan Herms,Stefan Herms,Janine Altmüller,Mohammad R. Toliat,Holger Thiele,Peter Nürnberg,Christian Wilhelm,Ulrich Stephani,Ingo Helbig,Holger Lerche,Fritz Zimprich,Bernd A. Neubauer,Saskia Biskup,Saskia Biskup,Sarah von Spiczak +73 more
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TLDR
Results establish alterations of the gene encoding the NMDA receptor NR2A subunit as a major genetic risk factor for IFE.Abstract:
Idiopathic focal epilepsy (IFE) with rolandic spikes is the most common childhood epilepsy, comprising a phenotypic spectrum from rolandic epilepsy (also benign epilepsy with centrotemporal spikes, BECTS) to atypical benign partial epilepsy (ABPE), Landau-Kleffner syndrome (LKS) and epileptic encephalopathy with continuous spike and waves during slow-wave sleep (CSWS). The genetic basis is largely unknown. We detected new heterozygous mutations in GRIN2A in 27 of 359 affected individuals from 2 independent cohorts with IFE (7.5%; P = 4.83 × 10(-18), Fisher's exact test). Mutations occurred significantly more frequently in the more severe phenotypes, with mutation detection rates ranging from 12/245 (4.9%) in individuals with BECTS to 9/51 (17.6%) in individuals with CSWS (P = 0.009, Cochran-Armitage test for trend). In addition, exon-disrupting microdeletions were found in 3 of 286 individuals (1.0%; P = 0.004, Fisher's exact test). These results establish alterations of the gene encoding the NMDA receptor NR2A subunit as a major genetic risk factor for IFE.read more
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Journal ArticleDOI
Altered EEG markers of synaptic plasticity in a human model of NMDA receptor deficiency: Anti-NMDA receptor encephalitis.
Silvano R. Gefferie,Angelina Maric,Hanne Critelli,S. Gueden,Gerhard Kurlemann,Salome Kurth,Margherita Nosadini,Barbara Plecko,Maya Ringli,Kevin Rostasy,Stefano Sartori,Bernhard Schmitt,Agnese Suppiej,Patrick Van Bogaert,Flavia M. Wehrle,Reto Huber,Bigna K. Bölsterli +16 more
TL;DR: In this article, the authors investigated whether pediatric patients with anti-NMDAR encephalitis, being a very rare but unique human model of NMDAR deficiency due to autoantibodies against receptor subunits, indeed show alterations in this sleep EEG marker for synaptic plasticity.
Journal ArticleDOI
Synaptic Dysfunction by Mutations in GRIN2B: Influence of Triheteromeric NMDA Receptors on Gain-of-Function and Loss-of-Function Mutant Classification
Marwa Elmasri,James S Lotti,Wajeeha Aziz,Oliver W. Steele,Eirini Karachaliou,Kenji Sakimura,Kasper B. Hansen,Andrew C. Penn +7 more
TL;DR: It is demonstrated that functional incorporation of GoF and LoF GluN2B mutants into synaptic receptors and the effects on EPSC decay times are highly dependent on the presence of triheteromeric GLUN1/2A/2B NMDA receptors, thereby influencing the functional classification of NMDA receptor variants as GoF or LoF mutations.
Journal ArticleDOI
Ipsilateral cortical motor desynchronisation is reduced in Benign Epilepsy with Centro-Temporal Spikes
Lisa Brindley,Loes Koelewijn,Amanda Kirby,Natalie Williams,Marie Thomas,Johann te Water-Naudé,Frances Gibbon,Suresh D. Muthukumaraswamy,Krish D. Singh,Khalid Hamandi,Khalid Hamandi +10 more
TL;DR: Altered movement-related oscillatory responses in ipsilateral motor cortex were associated with motor skill deficits in children with BECTS, and changes were more marked in those with more recent seizures.
Journal ArticleDOI
Sleep and Epilepsy, Clinical Spectrum and Updated Review.
TL;DR: In this paper, a review examines the epilepsy types and syndromes whose presentation is strongly influenced by the sleep state, with an appraisal about the role that sleep plays in facilitating seizures, while deleaneatign EEG findings and clinical manifestation.
Posted ContentDOI
Next-generation sequencing identifies novel gene variants and pathways involved in specific language impairment
Xiaowei Sylvia Chen,Rose H. Reader,Alexander Hoischen,Joris A. Veltman,Nuala H. Simpson,Clyde Francks,Dianne F. Newbury,Simon E. Fisher +7 more
TL;DR: This article performed whole exome sequencing of 43 unrelated probands affected by severe forms of specific language impairment, followed by independent validations with Sanger sequencing, and analyses of segregation patterns in parents and siblings, to try to shed new light on the aetiology of the disorder.
References
More filters
Journal ArticleDOI
A method and server for predicting damaging missense mutations.
Ivan Adzhubei,Steffen Schmidt,Leonid Peshkin,Vasily Ramensky,Anna Gerasimova,Peer Bork,Alexey S. Kondrashov,Shamil R. Sunyaev +7 more
TL;DR: A new method and the corresponding software tool, PolyPhen-2, which is different from the early tool polyPhen1 in the set of predictive features, alignment pipeline, and the method of classification is presented and performance, as presented by its receiver operating characteristic curves, was consistently superior.
Journal ArticleDOI
Revised Terminology and Concepts for Organization of Seizures and Epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009
Anne T. Berg,Anne T. Berg,Samuel F. Berkovic,Martin J. Brodie,Jeffrey Buchhalter,J. Helen Cross,Walter van Emde Boas,Jerome Engel,Jacqueline A. French,Tracy A. Glauser,Gary W. Mathern,Solomon L. Moshé,Douglas R. Nordli,Perrine Plouin,Ingrid E. Scheffer +14 more
TL;DR: The International League Against Epilepsy (ILAE) Commission on Classification and Terminology has revised concepts, terminology, and approaches for classifying seizures and forms of epilepsy.
Journal ArticleDOI
MutationTaster evaluates disease-causing potential of sequence alterations
TL;DR: MutationTaster allows the efficient filtering of NGS data for alterations with high disease-causing potential and provides Perl scripts that can process data from all major platforms (Roche 454, Illumina Genome Analyzer and ABI SOLiD).
Journal ArticleDOI
Strategies for multilocus linkage analysis in humans.
TL;DR: The results show that considerable economy and efficiency can be brought to the mapping endeavor by resorting to appropriate strategies of detecting linkage and by constructing the human genetic map on a common reference panel of families.
Journal ArticleDOI
Human Splicing Finder: an online bioinformatics tool to predict splicing signals
François Olivier Desmet,Dalil Hamroun,Marine Lalande,Gwenaëlle Collod-Béroud,Mireille Claustres,Christophe Béroud +5 more
TL;DR: Human Splicing Finder is designed, a tool to predict the effects of mutations on splicing signals or to identify splicing motifs in any human sequence, and it is shown that the mutation effect was correctly predicted in almost all cases.
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