TY - JOUR
T1 - Analysis of nuclear export sequence regions of FUS-related RNA-binding proteins in Essential tremor
AU - Lorenzo-Betancor, Oswaldo
AU - Ogaki, Kotaro
AU - Soto-Ortolaza, Alexandra
AU - Labbé, Catherine
AU - Ell, Carles Vilariño Gü
AU - Rajput, Alex
AU - Rajput, Ali H.
AU - Pastor, Pau
AU - Ortega, Sara
AU - Lorenzo, Elena
AU - Strongosky, Audrey J.
AU - Van Gerpen, Jay A.
AU - Uitti, Ryan J.
AU - Wszolek, Zbigniew K.
AU - Ross, Owen A.
N1 - Publisher Copyright:
© 2014 Lorenzo-Betancor et al.
PY - 2014/11/6
Y1 - 2014/11/6
N2 - Background and Objective: Genes encoding RNA-binding proteins, including FUS and TDP43, play a central role in different neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Recently, a mutation located in the nuclear export signal (NES) of the FUS gene has been reported to cause an autosomal dominant form of familial Essential tremor.Material and Methods: We sequenced the exons coding the NES domains of five RNA-binding proteins (TARDBP, hnRNPA2B1, hnRNPA1, TAF15 and EWSR1) that have been previously implicated in neurodegeneration in a series of 257 essential tremor (ET) cases and 376 healthy controls. We genotyped 404 additional ET subjects and 510 healthy controls to assess the frequency of the EWSR1 p.R471C substitution.Results: We identified a rare EWSR1 p.R471C substitution, which is highly conserved, in a single subject with familial ET. The pathogenicity of this substitution remains equivocal, as DNA samples from relatives were not available and the genotyping of 404 additional ET subjects did not reveal any further carriers. No other variants were observed with significant allele frequency differences compared to controls in the NES coding regions.Conclusions: The present study demonstrates that the NES domains of RNA-binding proteins are highly conserved. The role of the EWSR1 p.R471C substitution needs to be further evaluated in future studies.
AB - Background and Objective: Genes encoding RNA-binding proteins, including FUS and TDP43, play a central role in different neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Recently, a mutation located in the nuclear export signal (NES) of the FUS gene has been reported to cause an autosomal dominant form of familial Essential tremor.Material and Methods: We sequenced the exons coding the NES domains of five RNA-binding proteins (TARDBP, hnRNPA2B1, hnRNPA1, TAF15 and EWSR1) that have been previously implicated in neurodegeneration in a series of 257 essential tremor (ET) cases and 376 healthy controls. We genotyped 404 additional ET subjects and 510 healthy controls to assess the frequency of the EWSR1 p.R471C substitution.Results: We identified a rare EWSR1 p.R471C substitution, which is highly conserved, in a single subject with familial ET. The pathogenicity of this substitution remains equivocal, as DNA samples from relatives were not available and the genotyping of 404 additional ET subjects did not reveal any further carriers. No other variants were observed with significant allele frequency differences compared to controls in the NES coding regions.Conclusions: The present study demonstrates that the NES domains of RNA-binding proteins are highly conserved. The role of the EWSR1 p.R471C substitution needs to be further evaluated in future studies.
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U2 - 10.1371/journal.pone.0111989
DO - 10.1371/journal.pone.0111989
M3 - Article
C2 - 25375143
AN - SCOPUS:84910598592
SN - 1932-6203
VL - 9
JO - PloS one
JF - PloS one
IS - 11
M1 - e111989
ER -