Novel missense and truncating mutations in FUS/TLS in familial ALS

Background: Mutations in the FUS/TLS gene have been associated with familial amyotrophic lateral sclerosis (FALS). Methods: We analyzed the presence and frequency of C-terminal FUS/TLS mutations in a German amyotrophic lateral sclerosis (ALS) cohort, including 133 patients with sporadic ALS (SALS) and 58 patients with FALS by sequence analysis of exons 13–15. Results: We identified 2 novel heterozygous FUS/TLS mutations in 4 German ALS families including the novel missense mutation K510R and the truncating mutation R495X. The truncating mutation was associated with an aggressive disease course whereas the K510R mutation showed a mild phenotype with disease duration ranging from 6 to 8 years. No mutation was detected in 133 patients with SALS. Conclusions: Mutations in FUS/TLS account for 7% (4 of 58) of FALS in our German cohort.