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Genetic analysis of the FUS / TLS gene in essential tremor
Author(s) -
Parmalee N.,
Mirzozoda K.,
Kisselev S.,
Merner N.,
Dion P.,
Rouleau G.,
Clark L.,
Louis E. D.
Publication year - 2013
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.12023
Subject(s) - snp , genetics , amyotrophic lateral sclerosis , exon , genotyping , gene , exome sequencing , medicine , haplotype , mutation , single nucleotide polymorphism , biology , genotype , pathology , disease
Background and purpose Although essential tremor ( ET ) has a genetic basis, specific genes have not been identified. Recently, in a large ET family ( FET 1) from Q uebec, a non‐sense mutation (p. Q 290 X ) 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 C olumbia U niversity. 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 SNP s in the FUS / TLS gene by genotyping four haplotype tagging SNP s 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 FET 1 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 SNP s in FUS / TLS and ET was observed, and none of the analyzed SNP s 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 N orth A merica. We did not find evidence that the FUS / TLS gene is a risk factor for ET .