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

• Verfasst von: Yılmaz, Rüstem [VerfasserIn]
• Verfasst von: Grehl, Torsten [VerfasserIn]
• Verfasst von: Eckrich, Lukas [VerfasserIn]
• Verfasst von: Marschalkowski, Ines [VerfasserIn]
• Verfasst von: Weishaupt, Kanchi [VerfasserIn]
• Verfasst von: Valkadinov, Ivan [VerfasserIn]
• Verfasst von: Simic, Melita [VerfasserIn]
• Verfasst von: Brenner, David [VerfasserIn]
• Verfasst von: Andersen, Peter M. [VerfasserIn]
• Verfasst von: Wolf, Joachim [VerfasserIn]
• Verfasst von: Weishaupt, Jochen H. [VerfasserIn]
• Titel: Frequency of C9orf72 and SOD1 mutations in 302 sporadic ALS patients from three German ALS centers
• Verf.angabe: Rüstem Yilmaz, Torsten Grehl, Lukas Eckrich, Ines Marschalkowski, Kanchi Weishaupt, Ivan Valkadinov, Melita Simic, David Brenner, Peter M. Andersen, Joachim Wolf & Jochen H. Weishaupt
• E-Jahr: 2023
• Jahr: 17 Jan 2023
• Umfang: 6 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 30.09.2024
• Titel Quelle: Enthalten in: Amyotrophic lateral sclerosis & frontotemporal degeneration
• Ort Quelle: Abingdon : Taylor Francis Group, 2013
• Jahr Quelle: 2023
• Band/Heft Quelle: 24(2023), 5/6, Seite 414-419
• ISSN Quelle: 2167-9223
• DOI: doi:10.1080/21678421.2023.2165946
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Amyotrophic lateral sclerosis
• Sach-SW: motor neuron disease
• Sach-SW: neurodegeneration
• Sach-SW: neurogenetics
• Sach-SW: sporadic ALS
• K10plus-PPN: 1903716411

Abstract

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.