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Wagner, M. ; Lorenz, G.* ; Volk, A.E.* ; Brunet, T. ; Edbauer, D.* ; Berutti, R. ; Zhao, C. ; Anderl-Straub, S.* ; Bertram, L.* ; Danek, A.* ; Deschauer, M.* ; Dill, V.* ; Fassbender, K.* ; Fliessbach, K.* ; Götze, K.S.* ; Jahn, H.* ; Kornhuber, J.* ; Landwehrmeyer, B.* ; Lauer, M.* ; Obrig, H.* ; Prudlo, J.* ; Schneider, A.* ; Schroeter, M.L.* ; Uttner, I.* ; Vukovich, R.* ; Wiltfang, J.* ; Winkler, A.S.* ; Zhou, Q.* ; Ludolph, A.C.* ; Oexle, K. ; Otto, M.* ; Diehl-Schmid, J.* ; Winkelmann, J.

Clinico-genetic findings in 509 frontotemporal dementia patients.

Mol. Psychiatry, DOI: 10.1038/s41380-021-01271-2 (2021)
Publ. Version/Full Text Research data DOI PMC
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Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. To which extent genetic aberrations dictate clinical presentation remains elusive. We investigated the spectrum of genetic causes and assessed the genotype-driven differences in biomarker profiles, disease severity and clinical manifestation by recruiting 509 FTD patients from different centers of the German FTLD consortium where individuals were clinically assessed including biomarker analysis. Exome sequencing as well as C9orf72 repeat analysis were performed in all patients. These genetic analyses resulted in a diagnostic yield of 18.1%. Pathogenic variants in C9orf72 (n = 47), GRN (n = 26), MAPT (n = 11), TBK1 (n = 5), FUS (n = 1), TARDBP (n = 1), and CTSF (n = 1) were identified across all clinical subtypes of FTD. TBK1-associated FTD was frequent accounting for 5.4% of solved cases. Detection of a homozygous missense variant verified CTSF as an FTD gene. ABCA7 was identified as a candidate gene for monogenic FTD. The distribution of APOE alleles did not differ significantly between FTD patients and the average population. Male sex was weakly associated with clinical manifestation of the behavioral variant of FTD. Age of onset was lowest in MAPT patients. Further, high CSF neurofilament light chain levels were found to be related to GRN-associated FTD. Our study provides large-scale retrospective clinico-genetic data such as on disease manifestation and progression of FTD. These data will be relevant for counseling patients and their families.
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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 1359-4184
e-ISSN 1476-5578
Journal Molecular Psychiatry
Publisher Nature Publishing Group
Publishing Place Campus, 4 Crinan St, London, N1 9xw, England
Reviewing status Peer reviewed
Institute(s) Institute of Neurogenomics (ING)
Institute of Human Genetics (IHG)
POF-Topic(s) 30205 - Bioengineering and Digital Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-503200-001
G-500700-001
G-503292-001
Grants Deutsche Forschungsgemeinschaft (German Research Foundation)
DOI 10.1038/s41380-021-01271-2
WOS ID WOS:000698895800002
Scopus ID 85115833322
PubMed ID 34561610
Erfassungsdatum 2021-11-10
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