Browsing by Author "Bebek, Nerses"

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    Identification of epilepsy related pathways using genome-wide DNA methylation measures: A trio-based approach
    (PUBLIC LIBRARY SCIENCE, 2019-01-01) Ozdemir, Ozkan; Egemen, Ece; Iseri, Sibel Aylin Ugur; Sezerman, Osman Ugur; Bebek, Nerses; Baykan, Betul; Ozbek, Ugur
    Genetic generalized epilepsies (GGE) are genetically determined, as their name implies and they are clinically characterized by generalized seizures involving both sides of the brain in the absence of detectable brain lesions or other known causes. GGEs are yet complex and are influenced by many different genetic and environmental factors. Methylation specific epigenetic marks are one of the players of the complex epileptogenesis scenario leading to GGE. In this study, we have set out to perform genome-wide methylation profiling to analyze GGE trios each consisting of an affected parent-offspring couple along with an unaffected parent. We have developed a novel scoring scheme within trios to categorize each locus analyzed as hypo or hypermethylated. This stringent approach classified differentially methylated genes in each trio and helped us to produce trio specific and pooled gene lists with inherited and aberrant methylation levels. In order to analyze the methylation differences from a boarder perspective, we performed enrichment analysis with these lists using the PANOGA software. This collective effort has led us to detect pathways associated with the GGE phenotype, including the neurotrophin signaling pathway. We have demonstrated a trio based approach to genome-wide DNA methylation analysis that identified individual and possibly minor changes in methylation marks that could be involved in epileptogenesis leading to GGE.
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    Rare coding variants in genes encoding GABA(A) receptors in genetic generalised epilepsies: an exome-based case-control study
    (ELSEVIER SCIENCE INC, 2018-01-01) May, Patrick; Girard, Simon; Harrer, Merle; Bobbili, Dheeraj R.; Schubert, Julian; Wolking, Stefan; Becker, Felicitas; Lachance-Touchette, Pamela; Meloche, Caroline; Gravel, Micheline; Niturad, Cristina E.; Knaus, Julia; De Kovel, Carolien; Toliat, Mohamad; Polvi, Anne; Iacomino, Michele; Guerrero-Lopez, Rosa; Baulac, Stephanie; Marini, Carla; Thiele, Holger; Altmueller, Janine; Jabbari, Kamel; Ruppert, Ann-Kathrin; Jurkowski, Wiktor; Lal, Dennis; Rusconi, Raffaella; Cestele, Sandrine; Terragni, Benedetta; Coombs, Ian D.; Reid, Christopher A.; Striano, Pasquale; Caglayan, Hande; Siren, Auli; Everett, Kate; Moller, Rikke S.; Hjalgrim, Helle; Muhle, Hiltrud; Helbig, Ingo; Kunz, Wolfram S.; Weber, Yvonne G.; Weckhuysen, Sarah; De Jonghe, Peter; Sisodiya, Sanjay M.; Nabbout, Rima; Franceschetti, Silvana; Coppola, Antonietta; Vari, Maria S.; Trenite, Dorothee Kasteleijn-Nolst; Baykan, Betul; Ozbek, Ugur; Bebek, Nerses; Klein, Karl M.; Rosenow, Felix; Nguyen, Dang K.; Dubeau, Francois; Carmant, Lionel; Lortie, Anne; Desbiens, Richard; Clement, Jean-Francois; Cieuta-Walti, Cecile; Sills, Graeme J.; Auce, Pauls; Francis, Ben; Johnson, Michael R.; Marson, Anthony G.; Berghuis, Bianca; Sander, Josemir W.; Avbersek, Andreja; McCormack, Mark; Cavalleri, Gianpiero L.; Delanty, Norman; Depondt, Chantal; Krenn, Martin; Zimprich, Fritz; Peter, Sarah; Nikanorova, Marina; Kraaij, Robert; van Rooij, Jeroen; Balling, Rudi; Ikram, M. Arfan; Uitterlinden, Andre G.; Avanzini, Giuliano; Schorge, Stephanie; Petrou, Steven; Mantegazza, Massimo; Sander, Thomas; LeGuern, Eric; Serratosa, Jose M.; Koeleman, Bobby P. C.; Palotie, Aarno; Lehesjoki, Anna-Elina; Nothnagel, Michael; Nuernberg, Peter; Maljevic, Snezana; Zara, Federico; Cossette, Patrick; Krause, Roland; Lerche, Holger; Consortium, Epicure; Consortium, EuroEP.I.N.O.M.I.C.S. C. O. G. I. E.; Consortium, EpiPG. X.
    Background Genetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80\% in monozygotic twins, the genetic background is still poorly understood. We aimed to investigate the burden of rare genetic variants in genetic generalised epilepsy. Methods For this exome-based case-control study, we used three different genetic generalised epilepsy case cohorts and three independent control cohorts, all of European descent. Cases included in the study were clinically evaluated for genetic generalised epilepsy. Whole-exome sequencing was done for the discovery case cohort, a validation case cohort, and two independent control cohorts. The replication case cohort underwent targeted next-generation sequencing of the 19 known genes encoding subunits of GABA(A) receptors and was compared to the respective GABA(A) receptor variants of a third independent control cohort. Functional investigations were done with automated two-microelectrode voltage clamping in Xenopus laevis oocytes. Findings Statistical comparison of 152 familial index cases with genetic generalised epilepsy in the discovery cohort to 549 ethnically matched controls suggested an enrichment of rare missense (Nonsyn) variants in the ensemble of 19 genes encoding GABA(A) receptors in cases (odds ratio {[}OR] 2.40 {[}95\% CI 1.41-4.10]
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    SCREENING SLC2A1 GENE FOR SEQUENCE AND COPY NUMBER VARIATIONS ASSOCIATED WITH GLUT-1 DEFICIENCY SYNDROME
    (ISTANBUL UNIV, FAC MEDICINE, PUBL OFF, 2020-01-01) Ornek Erguzeloglu, Cemre; Kara, Bulent; Karacan, Ilker; Ozdemir, Ozkan; Kesim, Yesim; Bebek, Nerses; Ozbek, Ugur; Ugur Iseri, Sibel Aylin
    Objective: Glucose transporter-1 deficiency syndrome (GLUT1- DS) is defined as a metabolic encephalopathy that is associated with heterozygous and usually de novo pathogenic variations in the SLC2A1 (solute carrier family2 member1) gene. Materials and Methods: In this study, all coding exons and neighboring intronic regions of SLC2A1 were Sanger sequenced in 12 patients with clinically suspected GLUT1-DS. For de novo variations revealed after sequencing and segregation analysis, we also performed genome wide Single Nucleotide Polymor- phism (SNP) genotyping to confirm parental relatedness with the proband. In patients without any sequence variations, real-time quantitative real-time polymerase chain reaction (qPCR) was applied to determine the presence of any copy number variations (CNV). Results: Sanger sequencing followed by bioinformatics analysis, segregation in the family and SNP array genotyping revealed two novel and de novo pathogenic variations associated with the GLUT1-DS phenotype in 2 patients. qPCR results were compatible with one copy loss of SLC2A1 gene in another patient. All variations identified herein are likely to have caused null al-leles and resulted in GLUT1-DS through haplo insufficiency. Disscussion : In this study we used a series of molecular genetic approaches in order to identify all possible variations in SLC2A1 that may be associated with GLUT1-DS. This collective effort fa- cilitated diagnosis in 3 patients.
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    The COVID-19 from Neurological Overview
    (GALENOS PUBL HOUSE, 2020-01-01) Acar, Turkan; Demirel, Esra Aciman; Afsar, Nazire; Akcali, Aylin; Demir, Gulsen Akman; Alagoz, Aybala Neslihan; Mengi, Tugce Angin; Arsava, Ethem Murat; Ayta, Semih; Bebek, Nerses; Bilgic, Basar; Boz, Cavit; Cakar, Arman; Celebisoy, Nese; Cevik, Mehmet Ugur; Delen, Firuze; Tekce, Hacer Durmus; Ekmekci, Hakan; Elmali, Ayse Deniz; Erdinc, Oguz Osman; Erdogan, Fusun Ferda; Eren, Fettah; Ergun, Ufuk; Parman, Yesim Gulsen; Gumus, Haluk; Algin, Demet Ilhan; Karabudak, Rana; Karadas, Omer; Yildiz, Ozlem Kayim; Koc, Emine Rabia; Adapinar, Demet Ozbabalik; Ozdemir, Atilla Ozcan; Ozturk, Serefnur; Kocaman, Ayse Sagduyu; Sahin, Sevki; Topcuoglu, Esen Saka; Sener, Ozden; Tezer, F. Irsel; Togrol, Rifat Erdem; Tokcaer, Ayse Bora; Topcuoglu, Mehmet Akif; Tuncer, Nese; Uca, Ali Ulvi; Uluc, Kayihan; Yaka, Erdem; Yon, Mehmet Ilker