PloS one, 2014-11, Vol.9 (11), p.e111989
2014
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- Autor(en) / Beteiligte
- Titel
- Analysis of nuclear export sequence regions of FUS-Related RNA-binding proteins in essential tremor
- Ist Teil von
- PloS one, 2014-11, Vol.9 (11), p.e111989
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. 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. 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. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0111989Titel-ID: cdi_plos_journals_1979937591
- Format
- –
- Schlagworte
- Adult, Aged, Aged, 80 and over, Algorithms, Amino Acid Substitution, Amino acids, Amyotrophic lateral sclerosis, Binding proteins, Biology and Life Sciences, Brain research, Calmodulin-Binding Proteins - genetics, Coding, Degeneration, Deoxyribonucleic acid, Disease, DNA, Essential Tremor - genetics, Exons, Exports, Female, FLI-1 protein, Frontotemporal dementia, FUS gene, FUS protein, Gene frequency, Genes, Genetic Association Studies, Genetic Predisposition to Disease, Genomes, Genotype, Genotyping, Humans, Laboratories, Male, Medical research, Medicine and Health Sciences, Middle Aged, Mutation, Nervous system diseases, Neurodegeneration, Neurodegenerative diseases, Neurological diseases, Neurology, Neurosciences, Nuclear Export Signals, Nuclear transport, Nucleotide sequence, Pathogenicity, Pathogens, Protein binding, Proteins, Ribonucleic acid, RNA, RNA-binding protein, RNA-Binding Protein EWS, RNA-Binding Protein FUS - chemistry, RNA-Binding Protein FUS - metabolism, RNA-Binding Proteins - genetics, Sequence Analysis, DNA, Studies, Substitutes, Tremor