title: Novel missense and truncating mutations in FUS/TLS in familial ALS.
abstract: 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.
authors.affiliation: Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Waibel
authors.forename: M
authors.initials: M
authors.lastname: Neumann
authors.forename: M
authors.initials: M
authors.lastname: Rabe
authors.forename: T
authors.initials: T
authors.lastname: Meyer
authors.forename: A C
authors.initials: AC
authors.lastname: Ludolph
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000235:genetics*; D015331:Cohort Studies; D030541:Databases, Genetic; D005260:Female; D017353:Gene Deletion; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D034702:RNA-Binding Protein FUS / Q000235:genetics*
chemical_list: D034702:RNA-Binding Protein FUS