Exome sequencing identifies FUS mutations as a cause of essential tremor

Nancy D. Merner, Simon L. Girard, Hélène Catoire, Cynthia V. Bourassa, Véronique V. Belzil, Jean Baptiste Rivière, Pascale Hince, Annie Levert, Alexandre Dionne-Laporte, Dan Spiegelman, Anne Noreau, Sabrina Diab, Anna Szuto, Hélène Fournier, John Raelson, Majid Belouchi, Michel Panisset, Patrick Cossette, Nicolas Dupré, Geneviève BernardSylvain Chouinard, Patrick A. Dion, Guy A. Rouleau

Research output: Contribution to journalArticlepeer-review

124 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)313-319
Number of pages7
JournalAmerican journal of human genetics
Issue number2
StatePublished - Aug 10 2012

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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