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Wagner, Matias; Lorenz, Georg; Volk, Alexander E.; Brunet, Theresa; Edbauer, Dieter; Berutti, Riccardo; Zhao, Chen; Anderl-Straub, Sarah; Bertram, Lars; Danek, Adrian; Deschauer, Marcus; Dill, Veronika; Fassbender, Klaus; Fliessbach, Klaus; Götze, Katharina S.; Jahn, Holger; Kornhuber, Johannes; Landwehrmeyer, Bernhard; Lauer, Martin; Obrig, Hellmuth; Prudlo, Johannes; Schneider, Anja; Schroeter, Matthias L.; Uttner, Ingo; [...]

Clinico-genetic findings in 509 frontotemporal dementia patients

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  • Medientyp: E-Artikel
  • Titel: Clinico-genetic findings in 509 frontotemporal dementia patients
  • Beteiligte: Wagner, Matias; Lorenz, Georg; Volk, Alexander E.; Brunet, Theresa; Edbauer, Dieter; Berutti, Riccardo; Zhao, Chen; Anderl-Straub, Sarah; Bertram, Lars; Danek, Adrian; Deschauer, Marcus; Dill, Veronika; Fassbender, Klaus; Fliessbach, Klaus; Götze, Katharina S.; Jahn, Holger; Kornhuber, Johannes; Landwehrmeyer, Bernhard; Lauer, Martin; Obrig, Hellmuth; Prudlo, Johannes; Schneider, Anja; Schroeter, Matthias L.; Uttner, Ingo; [...]
  • Erschienen: Springer Science and Business Media LLC, 2021
  • Erschienen in: Molecular Psychiatry
  • Sprache: Englisch
  • DOI: 10.1038/s41380-021-01271-2
  • ISSN: 1359-4184; 1476-5578
  • Schlagwörter: Cellular and Molecular Neuroscience ; Psychiatry and Mental health ; Molecular Biology
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>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 <jats:italic>C9orf72</jats:italic> repeat analysis were performed in all patients. These genetic analyses resulted in a diagnostic yield of 18.1%. Pathogenic variants in <jats:italic>C9orf72</jats:italic> (<jats:italic>n</jats:italic> = 47), <jats:italic>GRN</jats:italic> (<jats:italic>n</jats:italic> = 26), <jats:italic>MAPT</jats:italic> (<jats:italic>n</jats:italic> = 11), <jats:italic>TBK1</jats:italic> (<jats:italic>n</jats:italic> = 5), <jats:italic>FUS</jats:italic> (<jats:italic>n</jats:italic> = 1)<jats:italic>, TARDBP</jats:italic> (<jats:italic>n</jats:italic> = 1), and <jats:italic>CTSF</jats:italic> (<jats:italic>n</jats:italic> = 1) were identified across all clinical subtypes of FTD. <jats:italic>TBK1</jats:italic>-associated FTD was frequent accounting for 5.4% of solved cases. Detection of a homozygous missense variant verified <jats:italic>CTSF</jats:italic> as an FTD gene. <jats:italic>ABCA7</jats:italic> 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 <jats:italic>MAPT</jats:italic> patients. Further, high CSF neurofilament light chain levels were found to be related to <jats:italic>GRN</jats:italic>-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.</jats:p>