title: Identification of FUS p.R377W in essential tremor.
abstract: OBJECTIVE
  Exome sequencing analysis has recently identified a nonsense mutation in fused in sarcoma (FUS) segregating with essential tremor (ET) within a large French-Canadian family. Further characterization of FUS resulted in the identification of additional mutations in ET patients; however, their pathogenicity still remains to be confirmed. The role of FUS in an independent cohort of ET patients from Canada was evaluated.
  
  
  METHODS
  The entire coding sequence of FUS in 217 patients diagnosed with ET was analyzed and two missense variants in 219 healthy controls were genotyped by Sanger sequencing.
  
  
  RESULTS
  Sequencing of FUS identified a previously reported non-pathogenic mutation p.G174_G175del in one ET patient and two healthy controls, and a novel p.R377W in one patient with family history of disease. This mutation is highly conserved and strongly predicted to be damaging by in silico analysis.
  
  
  CONCLUSIONS
  This study has identified a novel FUS p.R377W substitution in ET patients. Additional genotyping studies in a large number of ET patients and controls are necessary to conclusively define its pathogenicity.
authors.affiliation: Division of Neurology, University of Saskatchewan and Saskatoon Health Region, Saskatoon, SK, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Rajput
authors.forename: A H
authors.initials: AH
authors.lastname: Rajput
authors.forename: M L
authors.initials: ML
authors.lastname: Rajput
authors.forename: M
authors.initials: M
authors.lastname: Encarnacion
authors.forename: C Q
authors.initials: CQ
authors.lastname: Bernales
authors.forename: J P
authors.initials: JP
authors.lastname: Ross
authors.forename: M J
authors.initials: MJ
authors.lastname: Farrer
authors.forename: C
authors.initials: C
authors.lastname: Vilariño-Güell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020329:Essential Tremor / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D034702:RNA-Binding Protein FUS / Q000235:genetics*
chemical_list: D034702:RNA-Binding Protein FUS
keywords: FUS; amyotrophic lateral sclerosis; essential tremor; mutation