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

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. We aimed to determine the frequency of hexanucleotide repeat expansion (HRE) and mutations among patients in Germany with a diagnosis of sporadic or idiopathic ALS. : 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 and HRE. Pathological HRE results were confirmed in an independent laboratory. : In 302 patients with SALS, 27 (8.9%) patients with a HRE mutation were detected. Moreover, we identified two patients with a pathogenic mutation, one patient with a heterozygous p.D91A mutation in and three additional patients with rare variants not predicted to change the amino acid sequence. : According to our data, the proportion of SALS patients with mutations is in the expected range, whereas that with HRE is higher, suggesting a reduced penetrance. A considerable number of SALS patients can be amenable to gene-specific therapies.