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
Clinical Genetic Testing in Epilepsy
TL;DR: The types of tests available and the types of mutations that can be detected in epilepsy have greatly increased and application of genomic technologies in the clinical setting allows for more efficient genetic diagnosis in some patients.
Journal ArticleDOI
Sleep-Related Epilepsy
Mar Carreño,Santiago Fernández +1 more
TL;DR: Valproate, lamotrigine, topiramate, levetiracetam, and perampanel are effective against generalized tonic-clonic seizures in genetic generalized epilepsies, which frequently happen on awakening.
Journal ArticleDOI
Clinician's guide to genes associated with Rett-like phenotypes-Investigation of a Danish cohort and review of the literature.
Bitten Schönewolf-Greulich,A-M. Bisgaard,Rikke S. Møller,Morten Duno,Karen Brøndum-Nielsen,Simranpreet Kaur,N.J. Van Bergen,Sebastian Lunke,Stefanie Eggers,Cathrine Jespersgaard,John Christodoulou,Zeynep Tümer +11 more
TL;DR: A review of Rett‐like disorders with data from a Danish cohort of 35 patients with Rett-like phenotypes emphasizing the diagnostic overlap with Pitt‐Hopkins syndrome, Cornelia de Lange syndrome with SMC1A variants, and epileptic encephalopathies, for example, due to STXBP1 variants is combined.
Journal ArticleDOI
Frequency of CNKSR2 mutation in the X-linked epilepsy-aphasia spectrum.
John A. Damiano,Rosemary Burgess,Sara Kivity,Tally Lerman-Sagie,Zaid Afawi,Ingrid E. Scheffer,Ingrid E. Scheffer,Samuel F. Berkovic,Michael S. Hildebrand +8 more
TL;DR: In this paper, the frequency of CNKSR2 mutations in Ashkenazi Jewish families was found to be high in families with suspected X-linked epilepsy-aphasia spectrum (EAS) because of specific genetic counseling implications.
Journal ArticleDOI
GRIN2A mutations in epilepsy-aphasia spectrum disorders.
TL;DR: Epilepsy-aphasia spectrum (EAS) are a group of epilepsy syndromes denoting an association between epilepsy, speech disorders and the EEG signature of centrotemporal spikes, suggesting the possibility of other gene involved in the pathogenesis.
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