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| 001 | 139067 | ||
| 005 | 20240416115859.0 | ||
| 024 | 7 | _ | |a 10.1002/humu.23161 |2 doi |
| 024 | 7 | _ | |a pmid:28008748 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC5324646 |2 pmc |
| 024 | 7 | _ | |a 1059-7794 |2 ISSN |
| 024 | 7 | _ | |a 1098-1004 |2 ISSN |
| 024 | 7 | _ | |a altmetric:15149551 |2 altmetric |
| 037 | _ | _ | |a DZNE-2020-05389 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a van der Zee, Julie |b 0 |
| 245 | _ | _ | |a TBK1 Mutation Spectrum in an Extended European Patient Cohort with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis. |
| 260 | _ | _ | |a New York, NY [u.a.] |c 2017 |b Wiley-Liss |
| 264 | _ | 1 | |3 online |2 Crossref |b Wiley |c 2017-01-19 |
| 264 | _ | 1 | |3 print |2 Crossref |b Wiley |c 2017-03-01 |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1713192440_9657 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a 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. |
| 536 | _ | _ | |a 345 - Population Studies and Genetics (POF3-345) |0 G:(DE-HGF)POF3-345 |c POF3-345 |f POF III |x 0 |
| 536 | _ | _ | |a 344 - Clinical and Health Care Research (POF3-344) |0 G:(DE-HGF)POF3-344 |c POF3-344 |f POF III |x 1 |
| 542 | _ | _ | |i 2017-01-19 |2 Crossref |u http://doi.wiley.com/10.1002/tdm_license_1.1 |
| 542 | _ | _ | |i 2017-01-19 |2 Crossref |u http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 650 | _ | 7 | |a NF-kappa B |2 NLM Chemicals |
| 650 | _ | 7 | |a Protein-Serine-Threonine Kinases |0 EC 2.7.11.1 |2 NLM Chemicals |
| 650 | _ | 7 | |a TBK1 protein, human |0 EC 2.7.11.1 |2 NLM Chemicals |
| 650 | _ | 2 | |a Protein Serine-Threonine Kinases: genetics |2 MeSH |
| 650 | _ | 2 | |a Aged |2 MeSH |
| 650 | _ | 2 | |a Alleles |2 MeSH |
| 650 | _ | 2 | |a Amino Acid Substitution |2 MeSH |
| 650 | _ | 2 | |a Amyotrophic Lateral Sclerosis: diagnosis |2 MeSH |
| 650 | _ | 2 | |a Amyotrophic Lateral Sclerosis: epidemiology |2 MeSH |
| 650 | _ | 2 | |a Amyotrophic Lateral Sclerosis: genetics |2 MeSH |
| 650 | _ | 2 | |a Case-Control Studies |2 MeSH |
| 650 | _ | 2 | |a Cohort Studies |2 MeSH |
| 650 | _ | 2 | |a Enzyme Activation |2 MeSH |
| 650 | _ | 2 | |a European Continental Ancestry Group: genetics |2 MeSH |
| 650 | _ | 2 | |a Female |2 MeSH |
| 650 | _ | 2 | |a Frontotemporal Dementia: diagnosis |2 MeSH |
| 650 | _ | 2 | |a Frontotemporal Dementia: epidemiology |2 MeSH |
| 650 | _ | 2 | |a Frontotemporal Dementia: genetics |2 MeSH |
| 650 | _ | 2 | |a Genetic Association Studies |2 MeSH |
| 650 | _ | 2 | |a Heterozygote |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Male |2 MeSH |
| 650 | _ | 2 | |a Middle Aged |2 MeSH |
| 650 | _ | 2 | |a Mutation |2 MeSH |
| 650 | _ | 2 | |a NF-kappa B: metabolism |2 MeSH |
| 650 | _ | 2 | |a Phenotype |2 MeSH |
| 650 | _ | 2 | |a Protein-Serine-Threonine Kinases: genetics |2 MeSH |
| 650 | _ | 2 | |a Protein-Serine-Threonine Kinases: metabolism |2 MeSH |
| 650 | _ | 2 | |a Sequence Deletion |2 MeSH |
| 650 | _ | 2 | |a Protein Serine-Threonine Kinases: metabolism |2 MeSH |
| 650 | _ | 2 | |a White People: genetics |2 MeSH |
| 700 | 1 | _ | |a Gijselinck, Ilse |b 1 |
| 700 | 1 | _ | |a Van Mossevelde, Sara |b 2 |
| 700 | 1 | _ | |a Perrone, Federica |b 3 |
| 700 | 1 | _ | |a Dillen, Lubina |b 4 |
| 700 | 1 | _ | |a Heeman, Bavo |b 5 |
| 700 | 1 | _ | |a Bäumer, Veerle |b 6 |
| 700 | 1 | _ | |a Engelborghs, Sebastiaan |b 7 |
| 700 | 1 | _ | |a De Bleecker, Jan |b 8 |
| 700 | 1 | _ | |a Baets, Jonathan |b 9 |
| 700 | 1 | _ | |a Gelpi, Ellen |b 10 |
| 700 | 1 | _ | |a Rojas-García, Ricardo |b 11 |
| 700 | 1 | _ | |a Clarimón, Jordi |b 12 |
| 700 | 1 | _ | |a Lleó, Alberto |b 13 |
| 700 | 1 | _ | |a Diehl-Schmid, Janine |0 P:(DE-HGF)0 |b 14 |
| 700 | 1 | _ | |a Alexopoulos, Panagiotis |b 15 |
| 700 | 1 | _ | |a Perneczky, Robert |0 P:(DE-HGF)0 |b 16 |
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| 700 | 1 | _ | |a Miltenberger-Miltényi, Gabriel |b 28 |
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| 700 | 1 | _ | |a Vandenberghe, Rik |b 36 |
| 700 | 1 | _ | |a De Jonghe, Peter |b 37 |
| 700 | 1 | _ | |a De Deyn, Peter P |b 38 |
| 700 | 1 | _ | |a Sleegers, Kristel |b 39 |
| 700 | 1 | _ | |a Cruts, Marc |b 40 |
| 700 | 1 | _ | |a Van Broeckhoven, Christine |0 P:(DE-HGF)0 |b 41 |e Corresponding author |
| 700 | 1 | _ | |a Goeman, Johan |b 42 |
| 700 | 1 | _ | |a Nuytten, Dirk |b 43 |
| 700 | 1 | _ | |a Smets, Katrien |b 44 |
| 700 | 1 | _ | |a Robberecht, Wim |b 45 |
| 700 | 1 | _ | |a Damme, Philip Van |b 46 |
| 700 | 1 | _ | |a Bleecker, Jan De |b 47 |
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| 700 | 1 | _ | |a Dermaut, Bart |b 49 |
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| 700 | 1 | _ | |a Willems, Christiana |b 57 |
| 700 | 1 | _ | |a Salmon, Eric |b 58 |
| 700 | 1 | _ | |a Pastor, Pau |b 59 |
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| 700 | 1 | _ | |a Fabrizi, Gian Maria |b 80 |
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