title: Investigating FUS variation in Parkinson's disease.
abstract: Mutations of the FUS gene were first reported to cause amyotrophic lateral sclerosis (ALS). Subsequent studies confirmed the role of mutations in ALS and also implicated them in frontotemporal dementia (FTD). Recently, through Next-Generation Exome sequencing approaches a mutation resulting in a substitution (p.Q290X) in the nuclear export domain of the FUS protein was nominated as a cause of autosomal dominant essential tremor (ET) in a large kindred. In addition, recent reports suggest a possible role for TDP-43 mutations in parkinsonism; TDP-43 is another RNA-binding protein implicated in ALS. Given these findings we investigated the role of FUS variants in Parkinson's disease (PD). We sequenced specific regions of the gene encoding three functional domains of the FUS protein in 702 patients with PD. Our sequencing study did not identify any novel non-synonymous variant that would appear to affect the subjects' susceptibility to Parkinson's disease. These findings and previous studies have shown that variants within the FUS gene are not a common cause of PD or ET, in comparison to their role in ALS.
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Labbé
authors.forename: Sruti
authors.initials: S
authors.lastname: Rayaprolu
authors.forename: Alexandra
authors.initials: A
authors.lastname: Soto-Ortolaza
authors.forename: Kotaro
authors.initials: K
authors.lastname: Ogaki
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Uitti
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D034702:RNA-Binding Protein FUS / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D034702:RNA-Binding Protein FUS
keywords: Amyotrophic lateral sclerosis; Essential tremor; FUS; Genetics; Movement disorders; Parkinson's disease