A Loss‐of‐Function Variant in the Human Histidyl‐t RNA Synthetase ( HARS ) Gene is Neurotoxic In Vivo
dc.contributor.author | Vester, Aimée | en_US |
dc.contributor.author | Velez‐ruiz, Gisselle | en_US |
dc.contributor.author | McLaughlin, Heather M. | en_US |
dc.contributor.author | Nisc Comparative Sequencing Program, nisc Comparative Sequencing Program | en_US |
dc.contributor.author | Lupski, James R. | en_US |
dc.contributor.author | Talbot, Kevin | en_US |
dc.contributor.author | Vance, Jeffery M. | en_US |
dc.contributor.author | Züchner, Stephan | en_US |
dc.contributor.author | Roda, Ricardo H. | en_US |
dc.contributor.author | Fischbeck, Kenneth H. | en_US |
dc.contributor.author | Biesecker, Leslie G. | en_US |
dc.contributor.author | Nicholson, Garth | en_US |
dc.contributor.author | Beg, Asim A. | en_US |
dc.contributor.author | Antonellis, Anthony | en_US |
dc.date.accessioned | 2013-01-03T19:45:33Z | |
dc.date.available | 2014-03-03T15:09:23Z | en_US |
dc.date.issued | 2013-01 | en_US |
dc.identifier.citation | Vester, Aimée ; Velez‐ruiz, Gisselle ; McLaughlin, Heather M.Nisc Comparative Sequencing Program, nisc Comparative Sequencing Program ; Lupski, James R.; Talbot, Kevin; Vance, Jeffery M.; Züchner, Stephan ; Roda, Ricardo H.; Fischbeck, Kenneth H.; Biesecker, Leslie G.; Nicholson, Garth; Beg, Asim A.; Antonellis, Anthony; (2013). "A Lossâ ofâ Function Variant in the Human Histidylâ t RNA Synthetase ( HARS ) Gene is Neurotoxic In Vivo." Human Mutation 34(1): 191-199. <http://hdl.handle.net/2027.42/95567> | en_US |
dc.identifier.issn | 1059-7794 | en_US |
dc.identifier.issn | 1098-1004 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/95567 | |
dc.description.abstract | Aminoacyl‐t RNA synthetases ( ARS s) are ubiquitously expressed enzymes responsible for ligating amino acids to cognate t RNA molecules. Mutations in four genes encoding an ARS have been implicated in inherited peripheral neuropathy with an axonal pathology, suggesting that all ARS genes are relevant candidates for disease in patients with related phenotypes. Here, we present results from a mutation screen of the histidyl‐t RNA synthetase ( HARS ) gene in a large cohort of patients with peripheral neuropathy. These efforts revealed a rare missense variant (c.410G>A/p.Arg137Gln) that resides at a highly conserved amino acid, represents a loss‐of‐function allele when evaluated in yeast complementation assays, and is toxic to neurons when expressed in a worm model. In addition to the patient with peripheral neuropathy, p.Arg137Gln HARS was detected in three individuals by genome‐wide exome sequencing. These findings suggest that HARS is the fifth ARS locus associated with axonal peripheral neuropathy. Implications for identifying ARS alleles in human populations and assessing them for a role in neurodegenerative phenotypes are discussed. | en_US |
dc.publisher | Wiley Periodicals, Inc. | en_US |
dc.publisher | Cold Spring Harbor Laboratory Press | en_US |
dc.subject.other | HARS | en_US |
dc.subject.other | Peripheral Neuropathy | en_US |
dc.subject.other | Aminoacyl‐T RNA Synthetases | en_US |
dc.subject.other | Neurotoxicity | en_US |
dc.title | A Loss‐of‐Function Variant in the Human Histidyl‐t RNA Synthetase ( HARS ) Gene is Neurotoxic In Vivo | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Genetics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.identifier.pmid | 22930593 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/95567/1/humu22210.pdf | |
dc.identifier.doi | 10.1002/humu.22210 | en_US |
dc.identifier.source | Human Mutation | en_US |
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dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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