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

Neurology. 2010 Aug 31;75(9):815-7. doi: 10.1212/WNL.0b013e3181f07e26. Epub 2010 Jul 21.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amyotrophic Lateral Sclerosis / diagnosis
  • Amyotrophic Lateral Sclerosis / genetics*
  • Cohort Studies
  • Databases, Genetic
  • Female
  • Gene Deletion
  • Genetic Carrier Screening
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense / genetics*
  • Pedigree
  • RNA-Binding Protein FUS / genetics*


  • RNA-Binding Protein FUS