FUS mutations dominate TBK1 mutations in FUS/TBK1 double-mutant ALS/FTD pedigrees
In: neurogenetics ; ISSN 1364-6745 1364-6753, 2021
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Zugriff:
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.
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FUS mutations dominate TBK1 mutations in FUS/TBK1 double-mutant ALS/FTD pedigrees
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Autor/in / Beteiligte Person: | Brenner, David ; Müller, Kathrin ; Lattante, Serena ; Yilmaz, Rüstem ; Knehr, Antje ; Freischmidt, Axel ; Ludolph, Albert C. ; Andersen, Peter M. ; Weishaupt, Jochen H. ; Heidelberg, Ruprecht-Karls-Universität |
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Zeitschrift: | neurogenetics ; ISSN 1364-6745 1364-6753, 2021 |
Veröffentlichung: | Springer Science and Business Media LLC, 2021 |
Medientyp: | academicJournal |
DOI: | 10.1007/s10048-021-00671-4 |
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