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Am J Hum Genet. 2012 Aug 10;91(2):313-9. doi: 10.1016/j.ajhg.2012.07.002. Epub 2012 Aug 2.

Exome sequencing identifies FUS mutations as a cause of essential tremor.

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1
Centre of Excellence in Neurosciences, Centre Hospitalier de l'Université de Montréal Research Center, Université de Montréal, Montréal, QC H2L 2W5, Canada.

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.

PMID:
22863194
PMCID:
PMC3415547
DOI:
10.1016/j.ajhg.2012.07.002
[Indexed for MEDLINE]
Free PMC Article
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