Abstract
BACKGROUND AND PURPOSE: Although essential tremor (ET) has a genetic basis, specific genes have not been identified. Recently, in a large ET family (FET1) from Quebec, a non-sense mutation (p.Q290X) in the amyotrophic lateral sclerosis (ALS) gene fused in sarcoma/translated in liposarcoma (FUS/TLS) was identified by exome sequencing. No confirmatory studies have been published. METHODS: Two-hundred and fifty-nine ET cases and 262 controls were enrolled in a study at Columbia University. We performed a comprehensive analysis of the FUS/TLS gene by sequencing all exons in a subsample of 116 ET cases with early-onset (≤40 years) ET. We evaluated an association between ET and SNPs in the FUS/TLS gene by genotyping four haplotype tagging SNPs in all 259 ET cases and 262 controls. Additionally, seven variants associated with ALS, two variants of unknown pathogenicity detected in ALS cases, eight mis-sense variants predicted to be damaging, and six rare variants were genotyped in these 259 ET cases and 262 controls. RESULTS: FUS/TLS mutations previously reported in ALS, the FET1 family, or novel mutations were not found in any of the 116 early-onset ET cases. In the case-control analyses, although the power of the performed associations was limited, no significant association between tagging SNPs in FUS/TLS and ET was observed, and none of the analyzed SNPs showed evidence of association with ET. CONCLUSION: Our study suggests that pathogenic mutations in FUS/TLS are rare in a sample of early-onset ET cases in North America. We did not find evidence that the FUS/TLS gene is a risk factor for ET.