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Identification of FUS p.R377W in essential tremor
Author(s) -
Rajput A.,
Rajput A. H.,
Rajput M. L.,
Encarnacion M.,
Bernales C. Q.,
Ross J. P.,
Farrer M. J.,
VilariñoGüell C.
Publication year - 2014
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.12231
Subject(s) - missense mutation , sanger sequencing , exome sequencing , medicine , nonsense mutation , genetics , nonsense , mutation , genotyping , essential tremor , pathogenicity , bioinformatics , biology , genotype , gene , physical medicine and rehabilitation , microbiology and biotechnology
Background and purpose Exome sequencing analysis has recently identified a nonsense mutation in fused in sarcoma ( FUS ) segregating with essential tremor ( ET ) within a large F rench‐ C anadian family. Further characterization of FUS resulted in the identification of additional mutations in ET patients; however, their pathogenicity still remains to be confirmed. The role of FUS in an independent cohort of ET patients from Canada was evaluated. Methods The entire coding sequence of FUS in 217 patients diagnosed with ET was analyzed and two missense variants in 219 healthy controls were genotyped by Sanger sequencing. Results Sequencing of FUS identified a previously reported non‐pathogenic mutation p. G 174_ G 175del in one ET patient and two healthy controls, and a novel p. R 377W in one patient with family history of disease. This mutation is highly conserved and strongly predicted to be damaging by in silico analysis. Conclusion This study has identified a novel FUS p.R377W substitution in ET patients. Additional genotyping studies in a large number of ET patients and controls are necessary to conclusively define its pathogenicity.