Web of Science: 49 citations, Scopus: 52 citations, Google Scholar: citations,
TBK1 Mutation Spectrum in an Extended European Patient Cohort with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis
van der Zee, Julie (University of Antwerp)
Gijselinck, Ilse (University of Antwerp)
Van Mossevelde, Sara (Antwerp University Hospital)
Perrone, Federica (University of Antwerp)
Dillen, Lubina (University of Antwerp)
Heeman, Bavo (University of Antwerp)
Bäumer, Veerle (University of Antwerp)
Engelborghs, Sebastiaan (Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken)
De Bleecker, Jan (University Hospital Ghent and University of Ghent)
Baets, Jonathan (Antwerp University Hospital)
Gelpi, Ellen (Neurological Tissue Bank of the Biobanc - Hospital Clinic-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS))
Rojas García, Ricardo (Universitat Autònoma de Barcelona)
Clarimon, Jordi (Institut d'Investigació Biomèdica Sant Pau)
Lleó Bisa, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Diehl-Schmid, Janine (Technische Universität München)
Alexopoulos, Panagiotis (Technische Universität München)
Perneczky, Robert (West London Mental Health Trust)
Synofzik, Matthis (German Research Center for Neurodegenerative Diseases (DZNE))
Just, Jennifer (German Research Center for Neurodegenerative Diseases (DZNE))
Schöls, Ludger (German Research Center for Neurodegenerative Diseases (DZNE))
Graff, Caroline (Karolinska University Hospital)
Thonberg, Håkan (Karolinska University Hospital)
Borroni, Barbara (University of Brescia)
Padovani, Alessandro (University of Brescia)
Jordanova, Albena (Medical University-Sofia)
Sarafov, Stayko (Medical University-Sofia)
Tournev, Ivailo (New Bulgarian University)
de Mendonça, Alexandre (University of Lisbon)
Miltenberger-Miltényi, Gabriel (University of Lisbon)
Simões do Couto, Frederico (University of Lisbon)
Ramirez, Alfredo (University of Cologne)
Jessen, Frank (German Center for Neurodegenerative Diseases (DZNE))
Heneka, Michael T. (University of Bonn)
Gómez-Tortosa, Estrella (Fundación Jiménez Díaz)
Danek, Adrian (German Center for Neurodegenerative Diseases (DZNE))
Cras, Patrick (Antwerp University Hospital)
Vandenberghe, Rik (University Hospitals Leuven)
De Jonghe, Peter (Antwerp University Hospital)
De Deyn, Peter P. (Hospital Network Antwerp)
Sleegers, Kristel (University of Antwerp)
Cruts, Marc (University of Antwerp)
Van Broeckhoven, Christine (University of Antwerp)
Goeman, Johan (Hospital Network Antwerp)
Nuytten, Dirk (Hospital Network Antwerp)
Smets, Katrien (Antwerp University Hospital)
Robberecht, Wim (University Hospitals Leuven Gasthuisberg)
Damme, Philip Van (University Hospitals Leuven Gasthuisberg)
Bleecker, Jan De (University Hospital Ghent)
Santens, Patrick (University Hospital Ghent)
Dermaut, Bart (University Hospital Ghent)
Versijpt, Jan (University Hospital Brussels)
Michotte, Alex (University Hospital Brussels)
Ivanoiu, Adrian (Saint-Luc University Hospital)
Deryck, Olivier (General Hospital Sint-Jan Brugge)
Bergmans, Bruno (General Hospital Sint-Jan Brugge)
Delbeck, Jean (General Hospital Sint-Maria)
Bruyland, Marc (General Hospital Glorieux Ronse)
Willems, Christiana (Jessa Hospital)
Salmon, Eric (University of Liège and Memory Clinic)
Pastor, Pau (CIBERNED Instituto de Salud Carlos III)
Ortega-Cubero, Sara (Deparment of Neurology, Complejo Asistencial Universitario de Palencia)
Benussi, Luisa (Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli)
Ghidoni, Roberta (Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli)
Binetti, Giuliano (MAC Memory Center and Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli)
Hernández, Isabel (Fundació ACE, Institut Català de Neurociències Aplicades)
Boada Rovira, Mercè (Fundació ACE, Institut Català de Neurociències Aplicades)
Ruiz Laza, Agustín (Fundació ACE, Institut Català de Neurociències Aplicades)
Sorbi, Sandro (Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence)
Nacmias, Benedetta (Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence)
Bagnoli, Silvia (Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence)
Sorbi, Sandro (IRCCS Don Carlo Gnocchi Scandicci)
Sánchez Valle, Raquel (Hospital Clínic, IDIBAPS)
Lladó, Albert (Hospital Clínic, IDIBAPS)
Santana, Isabel (University of Coimbra)
Rosário Almeida, Maria (University of Coimbra)
Frisoni, Giovanni B (Hôpitaux Universitaires de Genève et Université de Genève, Genève, Switzerland and IRCCS Fatebenefratelli)
Maetzler, Walter (Hertie Institute for Clinical Brain Research)
Matej, Radoslav (Thomayer Hospital, Prague and Charles University)
Fraidakis, Matthew J. (NeuroRARE Centre for Rare and Genetic Neurological & Neuromuscular Diseases & Neurogenetics)
Kovacs, Gabor G. (Medical University of Vienna)
Fabrizi, Gian Maria (University of Verona)
Testi, Silvia (University of Verona)
Universitat Autònoma de Barcelona

Date: 2017
Abstract: We investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2,538 patients with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or FTD plus ALS, ascertained within the European Early-Onset Dementia Consortium. We assessed pathogenicity of predicted protein-truncating mutations by measuring loss of RNA expression. Functional effect of in-frame amino acid deletions and missense mutations was further explored in vivo on protein level and in vitro by an NFκB-induced luciferase reporter assay and measuring phosphorylated TBK1. The protein-truncating mutations led to the loss of transcript through nonsense-mediated mRNA decay. For the in-frame amino acid deletions, we demonstrated loss of TBK1 or phosphorylated TBK1 protein. An important fraction of the missense mutations compromised NFκB activation indicating that at least some functions of TBK1 are lost. Although missense mutations were also present in controls, over three times more mutations affecting TBK1 functioning were found in the mutation fraction observed in patients only, suggesting high-risk alleles (P = 0. 03). Total mutation frequency for confirmed TBK1 LoF mutations in the European cohort was 0. 7%, with frequencies in the clinical subgroups of 0. 4% in FTD, 1. 3% in ALS, and 3. 6% in FTD-ALS.
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. Creative Commons
Language: Anglès
Document: article ; recerca ; publishedVersion
Subject: TANK-Binding Kinase 1 ; TBK1 ; Frontotemporal dementia ; FTD ; Amyotrophic lateral sclerosis ; ALS ; Mutations ; NFκB luciferase reporter assay
Published in: Human Mutation, Vol. 38, Issue 3 (March 2017) , p. 297-309, ISSN 1098-1004

DOI: 10.1002/humu.23161
PMID: 28008748

13 p, 955.5 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació Biomèdica Sant Pau
Articles > Research articles
Articles > Published articles

 Record created 2018-02-07, last modified 2020-12-22

   Favorit i Compartir