FUS mutations dominate TBK1 mutations in FUS/TBK1 double-mutant ALS/FTD pedigrees

David Brenner, Kathrin Müller, Serena Lattante, Rüstem Yilmaz, Antje Knehr, Axel Freischmidt, Albert C. Ludolph, Peter M. Andersen, Jochen H. Weishaupt

Risultato della ricerca: Contributo in rivistaArticolo in rivista


Mutations in FUS and TBK1 often cause aggressive early-onset amyotrophic lateral sclerosis (ALS) or a late-onset ALS and/or frontotemporal dementia (FTD) phenotype, respectively. Co-occurrence of mutations in two or more Mendelian ALS/FTD genes has been repeatedly reported. However, little is known how two pathogenic ALS/FTD mutations in the same patient interact to shape the final phenotype. We screened 28 ALS patients with a known FUS mutation by whole-exome sequencing and targeted evaluation for mutations in other known ALS genes followed by genotype–phenotype correlation analysis of FUS/TBK1 double-mutant patients. We report on new and summarize previously published FUS and TBK1 double-mutant ALS/FTD patients and their families. We found that, within a family, mutations in FUS cause ALS while TBK1 single mutations are observed in FTD patients. FUS/TBK1 double mutations manifested as ALS and without a manifest difference regarding age at onset and disease duration when compared to FUS single-mutant individuals. In conclusion, TBK1 and FUS variants do not seem to interact in a simple additive way. Rather, the phenotype of FUS/TBK1 double-mutant patients appears to be dominated by the FUS mutation.
Lingua originaleEnglish
pagine (da-a)59-65
Numero di pagine7
Stato di pubblicazionePubblicato - 2022


  • ALS
  • Amyotrophic lateral sclerosis
  • FTD
  • FUS
  • Frontotemporal dementia
  • TBK1


Entra nei temi di ricerca di 'FUS mutations dominate TBK1 mutations in FUS/TBK1 double-mutant ALS/FTD pedigrees'. Insieme formano una fingerprint unica.

Cita questo