title: Exome sequencing identifies FUS mutations as a cause of essential tremor.
abstract: Essential tremor (ET) is a common neurodegenerative disorder that is characterized by a postural or motion tremor. Despite a strong genetic basis, a gene with rare pathogenic mutations that cause ET has not yet been reported. We used exome sequencing to implement a simple approach to control for misdiagnosis of ET, as well as phenocopies involving sporadic and senile ET cases. We studied a large ET-affected family and identified a FUS p.Gln290(∗) mutation as the cause of ET in this family. Further screening of 270 ET cases identified two additional rare missense FUS variants. Functional considerations suggest that the pathogenic effects of ET-specific FUS mutations are different from the effects observed when FUS is mutated in amyotrophic lateral sclerosis cases; we have shown that the ET FUS nonsense mutation is degraded by the nonsense-mediated-decay pathway, whereas amyotrophic lateral sclerosis FUS mutant transcripts are not.
authors.affiliation: Centre of Excellence in Neurosciences, Centre Hospitalier de l'Université de Montréal Research Center, Université de Montréal, Montréal, QC H2L 2W5, Canada.
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Merner
authors.forename: Simon L
authors.initials: SL
authors.lastname: Girard
authors.forename: Hélène
authors.initials: H
authors.lastname: Catoire
authors.forename: Cynthia V
authors.initials: CV
authors.lastname: Bourassa
authors.forename: Véronique V
authors.initials: VV
authors.lastname: Belzil
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Rivière
authors.forename: Pascale
authors.initials: P
authors.lastname: Hince
authors.forename: Annie
authors.initials: A
authors.lastname: Levert
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dionne-Laporte
authors.forename: Dan
authors.initials: D
authors.lastname: Spiegelman
authors.forename: Anne
authors.initials: A
authors.lastname: Noreau
authors.forename: Sabrina
authors.initials: S
authors.lastname: Diab
authors.forename: Anna
authors.initials: A
authors.lastname: Szuto
authors.forename: Hélène
authors.initials: H
authors.lastname: Fournier
authors.forename: John
authors.initials: J
authors.lastname: Raelson
authors.forename: Majid
authors.initials: M
authors.lastname: Belouchi
authors.forename: Michel
authors.initials: M
authors.lastname: Panisset
authors.forename: Patrick
authors.initials: P
authors.lastname: Cossette
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupré
authors.forename: Geneviève
authors.initials: G
authors.lastname: Bernard
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chouinard
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Dion
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D001483:Base Sequence; D020329:Essential Tremor / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics; D011792:Quebec; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D034702:RNA-Binding Protein FUS