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Frequency of C9orf72 and SOD1 mutations in 302 sporadic ALS patients from three German ALS centers

Background: ALS patients with a negative family history (sporadic ALS, SALS) represent more than 90% of all ALS cases. In light of the gene-specific therapies that are currently in development for ALS, knowledge about the genetic landscape of SALS in Germany is urgently needed. Objectives: We aimed...

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Main Authors: Yılmaz, Rüstem (Author) , Grehl, Torsten (Author) , Eckrich, Lukas (Author) , Marschalkowski, Ines (Author) , Weishaupt, Kanchi (Author) , Valkadinov, Ivan (Author) , Simic, Melita (Author) , Brenner, David (Author) , Andersen, Peter M. (Author) , Wolf, Joachim (Author) , Weishaupt, Jochen H. (Author)
Format: Article (Journal)
Language:English
Published: 17 Jan 2023
In: Amyotrophic lateral sclerosis & frontotemporal degeneration
Year: 2023, Volume: 24, Issue: 5/6, Pages: 414-419
ISSN:2167-9223
DOI:10.1080/21678421.2023.2165946
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1080/21678421.2023.2165946
Verlag, kostenfrei, Volltext: https://www.tandfonline.com/doi/full/10.1080/21678421.2023.2165946
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Author Notes:Rüstem Yilmaz, Torsten Grehl, Lukas Eckrich, Ines Marschalkowski, Kanchi Weishaupt, Ivan Valkadinov, Melita Simic, David Brenner, Peter M. Andersen, Joachim Wolf & Jochen H. Weishaupt
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Summary:Background: ALS patients with a negative family history (sporadic ALS, SALS) represent more than 90% of all ALS cases. In light of the gene-specific therapies that are currently in development for ALS, knowledge about the genetic landscape of SALS in Germany is urgently needed. Objectives: We aimed to determine the frequency of C9orf72 hexanucleotide repeat expansion (HRE) and SOD1 mutations among patients in Germany with a diagnosis of sporadic or idiopathic ALS. Methods: We genotyped SALS patients from three German ALS centers. Sanger sequencing, fragment length analysis, and repeat-primed PCR technologies were used to detect mutations in SOD1 and C9orf72 HRE. Pathological C9orf72 HRE results were confirmed in an independent laboratory. Results: In 302 patients with SALS, 27 (8.9%) patients with a C9orf72 HRE mutation were detected. Moreover, we identified two patients with a pathogenic SOD1 mutation, one patient with a heterozygous p.D91A mutation in SOD1, and three additional patients with rare SOD1 variants not predicted to change the amino acid sequence. Conclusions: According to our data, the proportion of SALS patients with SOD1 mutations is in the expected range, whereas that with C9orf72 HRE is higher, suggesting a reduced penetrance. A considerable number of SALS patients can be amenable to gene-specific therapies.
Item Description:Gesehen am 30.09.2024
Physical Description:Online Resource
ISSN:2167-9223
DOI:10.1080/21678421.2023.2165946

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