18 results on '"Kocoglu, Cemile"'
Search Results
2. ERLIN1 mutations cause teenage-onset slowly progressive ALS in a large Turkish pedigree
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Tunca, Ceren, Akçimen, Fulya, Coşkun, Cemre, Gündoğdu-Eken, Aslı, Kocoglu, Cemile, Çevik, Betül, Bekircan-Kurt, Can Ebru, Tan, Ersin, and Başak, A. Nazlı
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- 2018
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3. Homozygous CAPN1 mutations causing a spastic-ataxia phenotype in 2 families
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Kocoglu, Cemile, Gundogdu, Asli, Kocaman, Gulsen, Kahraman-Koytak, Pinar, Uluc, Kayihan, Kiziltan, Gunes, Caglayan, Ahmet Okay, Bilguvar, Kaya, Vural, Atay, and Basak, A. Nazli
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- 2018
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4. TRIM25 mutation (p.C168*), coding for an E3 ubiquitin ligase, is a cause of early‐onset autosomal dominant dementia with amyloid load and parkinsonism.
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Gómez‐Tortosa, Estrella, Baradaran‐Heravi, Yalda, Dillen, Lubina, Choudhury, Nila Roy, Agüero Rabes, Pablo, Pérez‐Pérez, Julián, Kocoglu, Cemile, Sainz, M. José, Ruiz González, Alicia, Téllez, Raquel, Cremades‐Jimeno, Lucía, Cárdaba, Blanca, Van Broeckhoven, Christine, Michlewski, Gracjan, and van der Zee, Julie
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INTRODUCTION: Patients with familial early‐onset dementia (EOD) pose a unique opportunity for gene identification studies. METHODS: We present the phenotype and whole‐exome sequencing (WES) study of an autosomal dominant EOD family. Candidate genes were examined in a set of dementia cases and controls (n = 3712). Western blotting was conducted of the wild‐type and mutant protein of the final candidate. RESULTS: Age at disease onset was 60 years (range 56 to 63). The phenotype comprised mixed amnestic and behavioral features, and parkinsonism. Cerebrospinal fluid and plasma biomarkers, and a positron emission tomography amyloid study suggested Alzheimer's disease. WES and the segregation pattern pointed to a nonsense mutation in the TRIM25 gene (p.C168*), coding for an E3 ubiquitin ligase, which was absent in the cohorts studied. Protein studies supported a loss‐of‐function mechanism. DISCUSSION: This study supports a new physiopathological mechanism for brain amyloidosis. Furthermore, it extends the role of E3 ubiquitin ligases dysfunction in the development of neurodegenerative diseases. Highlights: A TRIM25 nonsense mutation (p.C168*) is associated with autosomal dominant early‐onset dementia and parkinsonism with biomarkers suggestive of Alzheimer's disease.TRIM25 protein studies support that the mutation exerts its effect through loss of function.TRIM25, an E3 ubiquitin ligase, is known for its role in the innate immune response but this is the first report of association with neurodegeneration.The role of TRIM25 dysfunction in development of amyloidosis and neurodegeneration merits a new line of research. [ABSTRACT FROM AUTHOR]
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- 2023
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5. TRIM25 mutation (p.C168*), coding for an E3 ubiquitin ligase, is a cause of early-onset autosomal dominant dementia with amyloid load and parkinsonism
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Gomez-Tortosa, Estrella, Baradaran-Heravi, Yalda, Dillen, Lubina, Roy Choudhury, Nila, Rabes, Pablo Agüero, Pérez-Pérez, Julián, Kocoglu, Cemile, José Sainz, M., González, Alicia Ruiz, Téllez, Raquel, Cremades-Jimeno, Lucía, Cárdaba, Blanca, Broeckhoven, Christine Van, Michlewski, Gracjan, van der Zee, Julie, and EU EOD Consortium
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E3 ubiquitin ligase ,early-onset autosomal dominant dementia ,family-based whole-exome sequencing study ,TRIM25 ,Human medicine ,Alzheimer’s disease - Abstract
IntroductionPatients with familial early-onset dementia (EOD) pose a unique opportunity for gene identification studies. MethodsWe present the phenotype and whole-exome sequencing (WES) study of an autosomal dominant EOD family. Candidate genes were examined in a set of dementia cases and controls (n = 3712). Western blotting was conducted of the wild-type and mutant protein of the final candidate. ResultsAge at disease onset was 60 years (range 56 to 63). The phenotype comprised mixed amnestic and behavioral features, and parkinsonism. Cerebrospinal fluid and plasma biomarkers, and a positron emission tomography amyloid study suggested Alzheimer's disease. WES and the segregation pattern pointed to a nonsense mutation in the TRIM25 gene (p.C168*), coding for an E3 ubiquitin ligase, which was absent in the cohorts studied. Protein studies supported a loss-of-function mechanism. DiscussionThis study supports a new physiopathological mechanism for brain amyloidosis. Furthermore, it extends the role of E3 ubiquitin ligases dysfunction in the development of neurodegenerative diseases. HighlightsA TRIM25 nonsense mutation (p.C168*) is associated with autosomal dominant early-onset dementia and parkinsonism with biomarkers suggestive of Alzheimer's disease.TRIM25 protein studies support that the mutation exerts its effect through loss of function.TRIM25, an E3 ubiquitin ligase, is known for its role in the innate immune response but this is the first report of association with neurodegeneration.The role of TRIM25 dysfunction in development of amyloidosis and neurodegeneration merits a new line of research.
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- 2022
6. Investigating the Endo-Lysosomal System in Major Neurocognitive Disorders Due to Alzheimer’s Disease, Frontotemporal Lobar Degeneration and Lewy Body Disease: Evidence for SORL1 as a Cross-Disease Gene
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Benussi, Luisa, primary, Longobardi, Antonio, additional, Kocoglu, Cemile, additional, Carrara, Matteo, additional, Bellini, Sonia, additional, Ferrari, Clarissa, additional, Nicsanu, Roland, additional, Saraceno, Claudia, additional, Bonvicini, Cristian, additional, Fostinelli, Silvia, additional, Zanardini, Roberta, additional, Catania, Marcella, additional, Moisse, Matthieu, additional, Van Damme, Philip, additional, Di Fede, Giuseppe, additional, Binetti, Giuliano, additional, Van Broeckhoven, Christine, additional, van der Zee, Julie, additional, and Ghidoni, Roberta, additional
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- 2021
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7. Vestibulo-ocular reflex impairment in SPG7 hereditary spastic paraplegia
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Akdal, Gülden, Koçoğlu, Koray, Koçoğlu, Cemile, Bora, Elçin, Nazlı Başak, Ayşe, and Michael Halmágyi, Gábor
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- 2021
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8. ATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalization
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Tazelaar, Gijs, Boeynaems, Steven, De Decker, Mathias, van Vugt, Joke, Kool, Lindy, Goedee, H Stephan, Mclaughlin, Russell, Sproviero, William, Iacoangeli, Alfredo, Moisse, Matthieu, Jacquemyn, Maarten, Daelemans, Dirk, Dekker, Annelot, van der Spek, Rick, Westeneng, Henk-Jan, Kenna, Kevin, Assialioui, Abdelilah, Da Silva, Nica, Millecamps, Stéphanie, Akçimen, Fulya, Al Khleifat, Ahmad, Al-Chalabi, Ammar, Andersen, Peter, Basak, A Nazli, Bauer, Denis, Blair, Ian, Brands, William, Byrne, Ross, Calvo, Andrea, Gonzalez, Yolanda Campos, Chio, Adriano, Cooper-Knock, Jonothan, Corcia, Philippe, Couratier, Philippe, De Carvalho, Mamede, Drory, Vivian, Eitan, Chen, Redondo, Alberto Garcia, Gellera, Cinzia, Glass, Jonathan, Gotkine, Marc, Hardiman, Orla, Hornstein, Eran, Kenna, Brandon, Kiernan, Matthew, Kocoglu, Cemile, Kooyman, Maarten, Landers, John, Alonso, Victoria López, Middelkoop, Bas, Mill, Jonathan, Mitne-Neto, Miguel, Mora Pardina, Jesus, Morrison, Karen, Pinto, Susana, Gromicho, Marta, Panadés, Monica Povedano, Pulit, Sara, Ratti, Antonia, Robberecht, Wim, Schellevis, Raymond, Shatunov, Aleksey, Shaw, Christopher, Shaw, Pamela, Silani, Vincenzo, Staiger, Christine, Ticozzi, Nicola, Tunca, Ceren, Twine, Nathalie, Van Damme, Philip, van den Berg, Leonard, van Doormaal, Perry, van Eijk, Kristel, van Es, Michael, van Rheenen, Wouter, Veldink, Jan, Visscher, Peter, Vourc’h, Patrick, Weber, Markus, Williams, Kelly, Wray, Naomi, Yang, Jian, Zatz, Mayana, Zhang, Katharine, Povedano, Mónica, Pardina, Jesus, Salachas, François, Pasterkamp, R Jeroen, Van Den Bosch, Ludo, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,Spinocerebellar Ataxia Type 1 ,amyotrophic lateral sclerosis ,Protein TDP-43 ,Disease Association ,Biology ,[SCCO]Cognitive science ,03 medical and health sciences ,0302 clinical medicine ,C9orf72 ,medicine ,Genetics ,trinucleotide repeat expansions ,Amyotrophic lateral sclerosis ,ComputingMilieux_MISCELLANEOUS ,AcademicSubjects/SCI01870 ,[SCCO.NEUR]Cognitive science/Neuroscience ,General Engineering ,DNA Repeat Expansion ,medicine.disease ,Phenotype ,030104 developmental biology ,DNA repeat expansion ,genetic association study ,Original Article ,AcademicSubjects/MED00310 ,Trinucleotide repeat expansion ,030217 neurology & neurosurgery ,Esclerosi lateral amiotròfica ,Genètica - Abstract
Increasingly, repeat expansions are being identified as part of the complex genetic architecture of amyotrophic lateral sclerosis. To date, several repeat expansions have been genetically associated with the disease: intronic repeat expansions in C9orf72, polyglutamine expansions in ATXN2 and polyalanine expansions in NIPA1. Together with previously published data, the identification of an amyotrophic lateral sclerosis patient with a family history of spinocerebellar ataxia type 1, caused by polyglutamine expansions in ATXN1, suggested a similar disease association for the repeat expansion in ATXN1. We, therefore, performed a large-scale international study in 11 700 individuals, in which we showed a significant association between intermediate ATXN1 repeat expansions and amyotrophic lateral sclerosis (P = 3.33 × 10−7). Subsequent functional experiments have shown that ATXN1 reduces the nucleocytoplasmic ratio of TDP-43 and enhances amyotrophic lateral sclerosis phenotypes in Drosophila, further emphasizing the role of polyglutamine repeat expansions in the pathophysiology of amyotrophic lateral sclerosis., Repeat expansions are being identified as part of the complex genetic architecture of amyotrophic lateral sclerosis. This study shows a significant association between intermediate ATXN1 repeat expansions and amyotrophic lateral sclerosis, possibly via mislocalization of TDP-43, further emphasizing the role of polyglutamine expansions in the pathophysiology of amyotrophic lateral sclerosis., Graphical Abstract Graphical Abstract
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- 2020
9. Revisiting The Complex Architecture Of Als In Turkey: Expanding Genotypes, Shared Phenotypes, Molecular Networks, And A Public Variant Database
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Tunca, Ceren, Seker, Tuncay, Akcimen, Fulya, Coskun, Cemre, Bayraktar, Elif, Palvadeau, Robin, Zor, Seyit, Kocoglu, Cemile, Kartal, Ece, Sen, Nesli Ece, Hamzeiy, Hamid, Erimis, Aslihan Ozoguz, Norman, Utku, Karakahya, Oguzhan, Olgun, Gulden, Akgun, Tahsin, Durmus, Hacer, Sahin, Erdi, Cakar, Arman, and Gursoy, Esra Baar
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The last decade has proven that amyotrophic lateral sclerosis (ALS) is clinically and genetically heterogeneous, and that the genetic component in sporadic cases might be stronger than expected. This study investigates 1,200 patients to revisit ALS in the ethnically heterogeneous yet inbred Turkish population. Familial ALS (fALS) accounts for 20% of our cases. The rates of consanguinity are 30% in fALS and 23% in sporadic ALS (sALS). Major ALS genes explained the disease cause in only 35% of fALS, as compared with similar to 70% in Europe and North America. Whole exome sequencing resulted in a discovery rate of 42% (53/127). Whole genome analyses in 623 sALS cases and 142 population controls, sequenced within Project MinE, revealed well-established fALS gene variants, solidifying the concept of incomplete penetrance in ALS. Genome-wide association studies (GWAS) with whole genome sequencing data did not indicate a new risk locus. Coupling GWAS with a coexpression network of disease-associated candidates, points to a significant enrichment for cell cycle- and division-related genes. Within this network, literature text-mining highlightsDECR1, ATL1, HDAC2, GEMIN4, andHNRNPA3as important genes. Finally, information on ALS-related gene variants in the Turkish cohort sequenced within Project MinE was compiled in the GeNDAL variant browser (www.gendal.org).
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- 2020
10. Exploration of the endo‐lysosomal pathway genes in frontotemporal dementia: The use of protein‐protein interaction networks to prioritize rare‐variant association analysis results
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Kocoglu, Cemile, primary, Manzoni, Claudia, additional, Ferrari, Raffaele, additional, Van Broeckhoven, Christine, additional, and van der Zee, Julie, additional
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- 2020
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11. Proper Interventions in a Newborn with Cerebro-Costo-Mandibular Syndrome
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Gundogdu, Asli, ULUÇ, KAYIHAN, KAHRAMAN KOYTAK, PINAR, Kocoglu, Cemile, Kocaman, Gulsen, Basak, A. Nazli, Vural, Atay, Bilguv, Kaya, Caglayan, Ahmet Okay, Kiziltan, Gunes, and SHARIFOV, RASUL
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lcsh:R5-920 ,Pediatrics ,medicine.medical_specialty ,business.industry ,Tanyeri Bayraktar B., Bayraktar S., Karacanoglu D., ARALAŞMAK A., UZUNER S., -Proper Interventions in a Newborn with Cerebro-Costo-Mandibular Syndrome-, BEZMIALEM SCIENCE, cilt.6, ss.77-79, 2018 ,General Engineering ,Psychological intervention ,Cerebro ,glossoptosis ,stomatognathic diseases ,stomatognathic system ,Cleft palate ,respiratory insufficiency ,medicine ,laryngeal mask airway ,palatal plate ,lcsh:Medicine (General) ,business - Abstract
Cerebro-costo-mandibular syndrome is characterized by severe micrognathia with glossoptosis, short to cleft soft palate, bell-shaped small thorax with gaps between the posterior ossified rib and anterior cartilaginous rib and postnatal growth and mental deficiency. We present the clinical course and the early aggressive treatment of a newborn diagnosed as cerebro-costo-mandibular syndrome. The management of the patients with this syndrome is important over the morbidity and mortality. Most babies died due to respiratory distress. Although brain anomalies are uncommon in cerebro-costo-mandibular syndrome, hypoxia may cause neurodevelopmental disorders. In this case report, we emphasize the importance of proper ventilation and feeding in patients with cerebro-costo-mandibular syndrome to maintain normal development. Multidisciplinary approach is essential in monitoring of these patients.
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- 2019
12. Association of NIPA1 repeat expansions with amyotrophic lateral sclerosis in a large international cohort
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Tazelaar, Gij SHP, Dekker, Annelot M, van Vugt, Joke JFA, van der Spek, Rick A, Westeneng, Henk-Jan, Kool, Lindy JBG, Kenna, Kevin P, van Rheenen, Wouter, Pulit, Sara L, McLaughlin, Russell L, Sproviero, William, Iacoangeli, Alfredo, Huebers, Annemarie, Brenner, David, Morrison, Karen E, Shaw, Pamela J, Shaw, Christopher E, Povedano Panades, Monica, Mora Pardina, Jesus S, Glass, Jonathan D, Hardiman, Orla, Al-Chalabi, Ammar, van Damme, Philip, Robberecht, Wim, Landers, John E, Ludolph, Albert C, Weishaupt, Jochen H, van den Berg, Leonard H, Veldink, Jan H, van Es, Michael A, Akcimen, Fulya, Al Khleifat, Ahmad, Andersen, Peter, Basak, A Nazli, Bauer, Denis C, Blair, Ian, Brands, William J, Byrne, Ross P, Calvo, Andrea, Gonzalez, Yolanda Campos, Chio, Adriano, Cooper-Knock, Jonothan, Corcia, Philippe, Couratier, Philippe, de Carvalho, Mamede, Drory, Vivian E, Eitan, Chen, Garcia Redondo, Alberto, Gellera, Cinzia, Gotkine, Marc, Hornstein, Eran, Kenna, Brendan, Kiernan, Matthew C, Kocoglu, Cemile, Kooyman, Maarten, Lopez Alonso, Victoria, Middelkoop, Bas, Mill, Jonathan, Mitne-Neto, Miguel, Moisse, Matthieu, Pinto, Susana C, Ratti, Antonia, Schellevis, Raymond D, Shatunov, Aleksey, Silani, Vincenzo, Staiger, Christine, Tazelaar, Gijs HP, Ticozzi, Nicola, Tunca, Ceren, Twine, Nathalie A, van Doormaal, Perry TC, van Eijk, Kristel R, Visscher, Peter M, Vourch, Patrick, Weber, Markus, Williams, Kelly L, Wray, Naomi, Yang, Jian, Zatz, Mayana, and Zhang, Katharine
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0301 basic medicine ,Oncology ,Male ,Aging ,Geriatrics & Gerontology ,Internationality ,Cohort Studies ,0302 clinical medicine ,Copy-number variation ,Amyotrophic lateral sclerosis ,Non-U.S. Gov't ,DNA Repeat Expansion ,General Neuroscience ,Research Support, Non-U.S. Gov't ,Amyotrophic Lateral Sclerosis/genetics ,GENOME ,Cohort ,Female ,Life Sciences & Biomedicine ,Cohort study ,medicine.medical_specialty ,Hereditary spastic paraplegia ,Neuroscience(all) ,NIPA1 ,Clinical Neurology ,HEREDITARY SPASTIC PARAPLEGIA ,Research Support ,Article ,03 medical and health sciences ,DNA Repeat Expansion/genetics ,Meta-Analysis as Topic ,Internal medicine ,Angelman syndrome ,medicine ,Journal Article ,Humans ,Membrane Proteins/genetics ,Genetic Association Studies ,Science & Technology ,business.industry ,Neurosciences ,Membrane Proteins ,Repeat expansion ,medicine.disease ,Ageing ,030104 developmental biology ,Logistic Models ,Neurosciences & Neurology ,Neurology (clinical) ,Geriatrics and Gerontology ,Peptides ,business ,Trinucleotide repeat expansion ,Peptides/genetics ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome 1) mutations are known to cause hereditary spastic paraplegia type 6, a neurodegenerative disease that phenotypically overlaps to some extent with amyotrophic lateral sclerosis (ALS). Previously, a genomewide screen for copy number variants found an association with rare deletions in NIPA1 and ALS, and subsequent genetic analyses revealed that long (or expanded) polyalanine repeats in NIPA1 convey increased ALS susceptibility. We set out to perform a large-scale replication study to further investigate the role of NIPA1 polyalanine expansions with ALS, in which we characterized NIPA1 repeat size in an independent international cohort of 3955 patients with ALS and 2276 unaffected controls and combined our results with previous reports. Meta-analysis on a total of 6245 patients with ALS and 5051 controls showed an overall increased risk of ALS in those with expanded (>8) GCG repeat length (odds ratio = 1.50, p = 3.8×10-5). Together with previous reports, these findings provide evidence for an association of an expanded polyalanine repeat in NIPA1 and ALS. ispartof: NEUROBIOLOGY OF AGING vol:74 ispartof: location:United States status: published
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- 2019
13. No association of CpG SNP rs9357140 with onset age in Belgian C9orf72 repeat expansion carriers
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Koçoğlu, Cemile, Gossye, Helena, Dillen, Lubina, Van Mossevelde, Sara, De Bleecker, Jan L., Vandenberghe, Rik, De Deyn, Peter P., Sleegers, Kristel, Cras, Patrick, Engelborghs, Sebastiaan, Van Broeckhoven, Christine, and van der Zee, Julie
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- 2021
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14. Phenotypic and Genotypic Analysis of Hereditary Ataxia Patients in Sakarya City, Turkey
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Sayan, Saadet, primary, Kotan, Dilcan, additional, Gundogdu Eken, Asli, additional, Sahbaz, Irmak, additional, Kocoglu, Cemile, additional, and Basak, A. Nazli, additional
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- 2017
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15. Turkish families with juvenile motor neuron disease broaden the phenotypic spectrum ofSPG11
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Iskender, Ceren, primary, Kartal, Ece, additional, Akcimen, Fulya, additional, Kocoglu, Cemile, additional, Ozoguz, Aslihan, additional, Kotan, Dilcan, additional, Eraksoy, Mefkure, additional, Parman, Yesim G., additional, and Basak, Ayse Nazli, additional
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- 2015
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16. TRIM25 nonsense mutation (p.C168*) as the probable cause of early‐onset autosomal dominant Alzheimer's disease.
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Gómez‐Tortosa, Estrella, Baradaran‐Heravi, Yalda, Dillen, Lubina, Agüero, Pablo, Sainz, María José, Pérez‐Pérez, Julián, Kocoglu, Cemile, Téllez, Raquel, Van Broeckhoven, Christine, and van der Zee, Julie
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Background: Patients with early‐onset dementia (EOD) often have a high genetic burden, and EOD kindreds with an autosomal dominant pattern of inheritance (ADPI) are particularly powerful for gene identification studies. Methods: We present the clinical phenotype and a whole‐exome sequencing (WES) study of a Spanish EOD family with ADPI, including five affected and two unaffected siblings. The proband case was negative for mutations in a Next Generation Sequencing panel of genes associated with neurodegenerative dementias. Candidate pathogenic mutations were prioritized according to frequency in population databases, impact/pathogenicity scores, and segregation (including a disease‐free second branch of the family). Final candidate genes were also examined in a set of Spanish‐origin FTD cases (n=583) and controls (n=493), plus in a Belgian WES dataset of AD (n=236) and FTD (n=269) cases. Results: Affected siblings had an average disease onset of 60.2 years (range 56‐63 years). Two had a behavioral rather than an amnestic phenotype, developing some psychotic features and significant parkinsonism after treatment with risperidone. However, CSF biomarkers in one patient were indicative of an AD pathology. WES was conducted in four affected and one unaffected siblings (all of them APOEε 4,4). Variant prioritization pointed to 16 candidate variants, including three loss of function variants, two in‐frame deletions, and 11 missense. Additional genetic analysis of another unaffected sibling, a fifth affected sibling with incipient disease, plus four unaffected relatives from the second branch narrowed the list to two candidate genes: TRIM25 (p.C186*, CADD score 36) and EEA1 (p.V693A, CADD 18.2). TRIM25 is a cytoplasmic protein that functions as an ubiquitin E3 ligase and is involved in the innate immune response, while EEA1 is an endosomal trafficking protein. Potentially pathogenic (CADD>20) rare variants were found in the studied populations in EEA1 (0,7‐3,8%; Spanish‐Belgian) and TRIM25 (0‐0,7%). All except one were missense variants of uncertain significance. Importantly, in TRIM25 which is highly intolerable for loss of function mutations, we identified one additional nonsense mutation in TRIM25 in a frontal‐type dementia case. Conclusion: We conclude that in this EOD family, the nonsense mutation in TRIM25 is the most likely causal mutation. [ABSTRACT FROM AUTHOR]
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- 2021
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17. Revisiting the complex architecture of ALS in Turkey: Expanding genotypes, shared phenotypes, molecular networks, and a public variant database
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Mehmet Ali Akalin, Cemre Coşkun, Oznur Tastan, Tahsin Akgün, Ersin Tan, Aslihan Ozoguz Erimis, Mustafa Ertas, Halil Atilla Idrisoglu, Aysun Soysal, Erdi Şahin, Hamid Hamzeiy, Yesim Parman, Filiz Koç, Başar Bilgiç, Hasmet Hanagasi, Arman Çakar, Esra Gürsoy, Feza Deymeer, Ece Kartal, Fikret Aysal, Seyit Zor, Gulsen Babacan Yildiz, Nilda Turgut, Baris Isak, Gulden Olgun, Robin Palvadeau, Cemile Kocoglu, Fulya Akçimen, Tuncay Seker, Ersen Kavak, Elif Bayraktar, Utku Norman, A. Nazli Basak, A. Ercument Cicek, Ceren Tunca, Oguzhan Karakahya, Piraye Oflazer, Nesli-Ece Sen, Nurten Uzun Adatepe, Kayihan Uluc, Hacer Durmus, Cavit Boz, Dilcan Kotan, BABACAN YILDIZ, GÜLSEN, Tunca, Ceren, Seker, Tuncay, Akcimen, Fulya, Coskun, Cemre, Bayraktar, Elif, Palvadeau, Robin, Zor, Seyit, Kocoglu, Cemile, Kartal, Ece, Sen, Nesli Ece, Hamzeiy, Hamid, Erimis, Aslihan Ozoguz, Norman, Utku, Karakahya, Oguzhan, Olgun, Gulden, Akgun, Tahsin, Durmus, Hacer, Sahin, Erdi, Cakar, Arman, Gursoy, Esra Baar, Yildiz, Gulsen Babacan, Isak, Baris, Uluc, Kayihan, Hanagasi, Hasmet, Bilgic, Basar, Turgut, Nilda, Aysal, Fikret, Ertas, Mustafa, Boz, Cavit, Kotan, Dilcan, Idrisoglu, Halil, Soysal, Aysun, Adatepe, Nurten Uzun, Akalin, Mehmet Ali, Koc, Filiz, Tan, Ersin, Oflazer, Piraye, Deymeer, Feza, Tastan, Oznur, Cicek, A. Ercument, Kavak, Ersen, Parman, Yesim, Basak, A. Nazli, Karakahya, Oğuzhan, Olgun, Gülden, Çiçek, A. Ercüment, and İÜC, Cerrahpaşa Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü
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Turkey ,Genome-wide association study ,Gene mutation ,AMYOTROPHIC-LATERAL-SCLEROSIS ,ALS variant database ,Cell-Cycle Regulators ,Databases, Genetic ,MOTOR-NEURON DISEASE ,Coexpression Network ,genetics ,Genetics (clinical) ,Exome sequencing ,Genetics ,next generation sequencing ,RISK ,0303 health sciences ,education.field_of_study ,Project MinE ,030305 genetics & heredity ,SPINAL MUSCULAR-ATROPHY ,Amyotrophic-Lateral-Sclerosis ,clinical exome sequencing ,Penetrance ,3. Good health ,Phenotype ,Spinal Muscular-Atrophy ,Turkish peninsula ,motor neuron disease ,COEXPRESSION NETWORK ,GENE-MUTATIONS ,FORM ,Risk ,Genotype ,Population ,Locus (genetics) ,Biology ,03 medical and health sciences ,Gene-Mutations ,Sequence Variation ,Analyses Identify ,coexpression network analysis ,SEQUENCE VARIATION ,Humans ,Expanding genotypes, shared phenotypes, molecular networks, and a public variant database-, HUMAN MUTATION, cilt.41, 2020 [Tunca C., Seker T., Akcimen F., Coskun C., Bayraktar E., Palvadeau R., Zor S., Kocoglu C., Kartal E., Sen N. E. , et al., -Revisiting the complex architecture of ALS in Turkey] ,education ,Form ,030304 developmental biology ,Genetic association ,Internet ,genome-wide association study ,Whole Genome Sequencing ,ANALYSES IDENTIFY ,Amyotrophic Lateral Sclerosis ,Motor-Neuron Disease ,CELL-CYCLE REGULATORS ,ALS - Abstract
Olgun, Gulden/0000-0002-4467-1610; Sahin, Erdi/0000-0002-5792-2888; Tastan, Oznur/0000-0001-7058-5372; Akcimen, Fulya/0000-0003-0931-5247; Kartal, Ece/0000-0002-7720-455X WOS:000542467300001 PubMed ID: 32579787 The last decade has proven that amyotrophic lateral sclerosis (ALS) is clinically and genetically heterogeneous, and that the genetic component in sporadic cases might be stronger than expected. This study investigates 1,200 patients to revisit ALS in the ethnically heterogeneous yet inbred Turkish population. Familial ALS (fALS) accounts for 20% of our cases. The rates of consanguinity are 30% in fALS and 23% in sporadic ALS (sALS). Major ALS genes explained the disease cause in only 35% of fALS, as compared with similar to 70% in Europe and North America. Whole exome sequencing resulted in a discovery rate of 42% (53/127). Whole genome analyses in 623 sALS cases and 142 population controls, sequenced within Project MinE, revealed well-established fALS gene variants, solidifying the concept of incomplete penetrance in ALS. Genome-wide association studies (GWAS) with whole genome sequencing data did not indicate a new risk locus. Coupling GWAS with a coexpression network of disease-associated candidates, points to a significant enrichment for cell cycle- and division-related genes. Within this network, literature text-mining highlightsDECR1, ATL1, HDAC2, GEMIN4, andHNRNPA3as important genes. Finally, information on ALS-related gene variants in the Turkish cohort sequenced within Project MinE was compiled in the GeNDAL variant browser (www.gendal.org). TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109S075]; Bogazici University Research FundsBogazici University [15B01P1]; Suna and Inan Kirac Foundation [2005-2020] TUBITAK, Grant/Award Number: 109S075; Bogazici University Research Funds, Grant/Award Number: 15B01P1; Suna and Inan Kirac Foundation, Grant/Award Number: 2005-2020
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- 2020
18. TRIM25 mutation (p.C168*), coding for an E3 ubiquitin ligase, is a cause of early-onset autosomal dominant dementia with amyloid load and parkinsonism.
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Gómez-Tortosa E, Baradaran-Heravi Y, Dillen L, Choudhury NR, Agüero Rabes P, Pérez-Pérez J, Kocoglu C, Sainz MJ, Ruiz González A, Téllez R, Cremades-Jimeno L, Cárdaba B, Van Broeckhoven C, Michlewski G, and van der Zee J
- Subjects
- Humans, Codon, Nonsense, Ubiquitin-Protein Ligases genetics, Ubiquitin-Protein Ligases metabolism, Amyloidogenic Proteins, Biomarkers, Tripartite Motif Proteins genetics, Transcription Factors genetics, Alzheimer Disease diagnostic imaging, Alzheimer Disease genetics, Dementia, Amyloidosis, Parkinsonian Disorders diagnostic imaging, Parkinsonian Disorders genetics
- Abstract
Introduction: Patients with familial early-onset dementia (EOD) pose a unique opportunity for gene identification studies., Methods: We present the phenotype and whole-exome sequencing (WES) study of an autosomal dominant EOD family. Candidate genes were examined in a set of dementia cases and controls (n = 3712). Western blotting was conducted of the wild-type and mutant protein of the final candidate., Results: Age at disease onset was 60 years (range 56 to 63). The phenotype comprised mixed amnestic and behavioral features, and parkinsonism. Cerebrospinal fluid and plasma biomarkers, and a positron emission tomography amyloid study suggested Alzheimer's disease. WES and the segregation pattern pointed to a nonsense mutation in the TRIM25 gene (p.C168*), coding for an E3 ubiquitin ligase, which was absent in the cohorts studied. Protein studies supported a loss-of-function mechanism., Discussion: This study supports a new physiopathological mechanism for brain amyloidosis. Furthermore, it extends the role of E3 ubiquitin ligases dysfunction in the development of neurodegenerative diseases., Highlights: A TRIM25 nonsense mutation (p.C168*) is associated with autosomal dominant early-onset dementia and parkinsonism with biomarkers suggestive of Alzheimer's disease. TRIM25 protein studies support that the mutation exerts its effect through loss of function. TRIM25, an E3 ubiquitin ligase, is known for its role in the innate immune response but this is the first report of association with neurodegeneration. The role of TRIM25 dysfunction in development of amyloidosis and neurodegeneration merits a new line of research., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
- Published
- 2023
- Full Text
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