% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{vanderZee:139067,
      author       = {van der Zee, Julie and Gijselinck, Ilse and Van Mossevelde,
                      Sara and Perrone, Federica and Dillen, Lubina and Heeman,
                      Bavo and Bäumer, Veerle and Engelborghs, Sebastiaan and De
                      Bleecker, Jan and Baets, Jonathan and Gelpi, Ellen and
                      Rojas-García, Ricardo and Clarimón, Jordi and Lleó,
                      Alberto and Diehl-Schmid, Janine and Alexopoulos, Panagiotis
                      and Perneczky, Robert and Synofzik, Matthis and Just,
                      Jennifer and Schöls, Ludger and Graff, Caroline and
                      Thonberg, Håkan and Borroni, Barbara and Padovani,
                      Alessandro and Jordanova, Albena and Sarafov, Stayko and
                      Tournev, Ivailo and de Mendonça, Alexandre and
                      Miltenberger-Miltényi, Gabriel and Simões do Couto,
                      Frederico and Ramirez, Alfredo and Jessen, Frank and Heneka,
                      Michael T and Gómez-Tortosa, Estrella and Danek, Adrian and
                      Cras, Patrick and Vandenberghe, Rik and De Jonghe, Peter and
                      De Deyn, Peter P and Sleegers, Kristel and Cruts, Marc and
                      Van Broeckhoven, Christine and Goeman, Johan and Nuytten,
                      Dirk and Smets, Katrien and Robberecht, Wim and Damme,
                      Philip Van and Bleecker, Jan De and Santens, Patrick and
                      Dermaut, Bart and Versijpt, Jan and Michotte, Alex and
                      Ivanoiu, Adrian and Deryck, Olivier and Bergmans, Bruno and
                      Delbeck, Jean and Bruyland, Marc and Willems, Christiana and
                      Salmon, Eric and Pastor, Pau and Ortega-Cubero, Sara and
                      Benussi, Luisa and Ghidoni, Roberta and Binetti, Giuliano
                      and Hernández, Isabel and Boada, Mercè and Ruiz, Agustín
                      and Sorbi, Sandro and Nacmias, Benedetta and Bagnoli, Silvia
                      and Sorbi, Sandro and Sanchez-Valle, Raquel and Llado,
                      Albert and Santana, Isabel and Rosário Almeida, Maria and
                      Frisoni, Giovanni B and Maetzler, Walter and Matej, Radoslav
                      and Fraidakis, Matthew J and Kovacs, Gabor G and Fabrizi,
                      Gian Maria and Testi, Silvia},
      title        = {{TBK}1 {M}utation {S}pectrum in an {E}xtended {E}uropean
                      {P}atient {C}ohort with {F}rontotemporal {D}ementia and
                      {A}myotrophic {L}ateral {S}clerosis.},
      journal      = {Human mutation},
      volume       = {38},
      number       = {3},
      issn         = {1059-7794},
      address      = {New York, NY [u.a.]},
      publisher    = {Wiley-Liss},
      reportid     = {DZNE-2020-05389},
      pages        = {297-309},
      year         = {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.},
      keywords     = {Protein Serine-Threonine Kinases: genetics / Aged / Alleles
                      / Amino Acid Substitution / Amyotrophic Lateral Sclerosis:
                      diagnosis / Amyotrophic Lateral Sclerosis: epidemiology /
                      Amyotrophic Lateral Sclerosis: genetics / Case-Control
                      Studies / Cohort Studies / Enzyme Activation / European
                      Continental Ancestry Group: genetics / Female /
                      Frontotemporal Dementia: diagnosis / Frontotemporal
                      Dementia: epidemiology / Frontotemporal Dementia: genetics /
                      Genetic Association Studies / Heterozygote / Humans / Male /
                      Middle Aged / Mutation / NF-kappa B: metabolism / Phenotype
                      / Protein-Serine-Threonine Kinases: genetics /
                      Protein-Serine-Threonine Kinases: metabolism / Sequence
                      Deletion / Protein Serine-Threonine Kinases: metabolism /
                      White People: genetics / NF-kappa B (NLM Chemicals) /
                      Protein-Serine-Threonine Kinases (NLM Chemicals) / TBK1
                      protein, human (NLM Chemicals)},
      cin          = {AG Gasser / AG Schöls / AG Jessen / AG Heneka ; AG Heneka
                      / U Clinical Researchers - München},
      ddc          = {610},
      cid          = {I:(DE-2719)1210000 / I:(DE-2719)5000005 /
                      I:(DE-2719)1011102 / I:(DE-2719)1011303 /
                      I:(DE-2719)7000003},
      pnm          = {345 - Population Studies and Genetics (POF3-345) / 344 -
                      Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-345 / G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28008748},
      pmc          = {pmc:PMC5324646},
      doi          = {10.1002/humu.23161},
      url          = {https://pub.dzne.de/record/139067},
}