{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:13:38Z","timestamp":1787508818214,"version":"build-2736575974"},"reference-count":59,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015668","name":"Ontario Ministry of Research and Innovation","doi-asserted-by":"publisher","award":["ER18\u201014\u2010183"],"award-info":[{"award-number":["ER18\u201014\u2010183"]}],"id":[{"id":"10.13039\/501100015668","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002790","name":"Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["04776"],"award-info":[{"award-number":["04776"]}],"id":[{"id":"10.13039\/501100002790","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002790","name":"Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["580214"],"award-info":[{"award-number":["580214"]}],"id":[{"id":"10.13039\/501100002790","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000030","name":"Institute of Genetics","doi-asserted-by":"publisher","award":["185961"],"award-info":[{"award-number":["185961"]}],"id":[{"id":"10.13039\/501100000030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Heterozygous pathogenic variants in the histidyl\u2010tRNA synthetase (\n                    <jats:italic>HARS<\/jats:italic>\n                    ) gene are associated with Charcot\u2013Marie\u2013Tooth (CMT) type 2W disease, classified as an axonal peripheral neuropathy. To date, at least 60 variants causing CMT symptoms have been identified in seven different aminoacyl\u2010tRNA synthetases, with eight being found in the catalytic domain of HARS. The genetic data clearly show a causative role of aminoacyl\u2010tRNA synthetases in CMT; however, the cellular mechanisms leading to pathology can vary widely and are unknown in the case of most identified variants. Here we describe a novel\n                    <jats:italic>HARS<\/jats:italic>\n                    variant, c.412T&gt;C; p.Y138H, identified through a CMT gene panel in a patient with peripheral neuropathy. To determine the effect of p.Y138H we employed a humanized HARS yeast model and recombinant protein biochemistry, which identified a deficiency in protein dimerization and a growth defect which shows mild but significant improvement with histidine supplementation. This raises the potential for a clinical trial of histidine.\n                  <\/jats:p>","DOI":"10.1002\/iub.2918","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T07:48:52Z","timestamp":1727768932000},"page":"1125-1138","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Characterization of a novel heterozygous variant in the histidyl\u2010\n                    <scp>tRNA<\/scp>\n                    synthetase gene associated with\n                    <scp>Charcot\u2013Marie\u2013Tooth<\/scp>\n                    disease type\n                    <scp>2W<\/scp>"],"prefix":"10.1002","volume":"76","author":[{"given":"Sarah D. P.","family":"Wilhelm","sequence":"first","affiliation":[{"name":"Department of Biochemistry The University of Western Ontario  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica A.","family":"Moresco","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Paediatrics The University of Western Ontario  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto D.","family":"Rivero","sequence":"additional","affiliation":[{"name":"Institute for Neurological Research (FLENI)  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria Mok","family":"Siu","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Paediatrics The University of Western Ontario  London Ontario Canada"},{"name":"Children's Health Research Institute  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1721-1667","authenticated-orcid":false,"given":"Ilka U.","family":"Heinemann","sequence":"additional","affiliation":[{"name":"Department of Biochemistry The University of Western Ontario  London Ontario Canada"},{"name":"Children's Health Research Institute  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103272"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2013.01.009"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000373"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-64076-5.00042-9"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20143419"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1693006"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.31"},{"key":"e_1_2_6_9_1","first-page":"1224","article-title":"Charcot\u2010Marie\u2010Tooth disease and other hereditary neuropathies","volume":"26","author":"Klein CJ","year":"2020","journal-title":"Continuum"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22166"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14020254"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/375039"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1727"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.12.005"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv158"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2013-305049"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1908288116"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcae070"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.67.4.550-573.2003"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0026-3"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.69.1.617"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.071720.119"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1423664112"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2017.06.012"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2013.02.002"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201600052"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx231"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2016.11.013"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6650"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2017.1379645"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.REV118.002982"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac239"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/gbe\/evv095"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01539922"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00525-9"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.1999.079"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr696"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1321312111"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes10030250"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.021311"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028936"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001091"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1153"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.52"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.9.8.677"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e13-01-0010"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2016.10.013"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.7b00114"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.21.8655"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1546312"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.78606"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12962"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22210"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15249"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.4c00142"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.25031"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01554-2021"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2019.146625"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/nqaa210"}],"container-title":["IUBMB Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iub.2918","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T07:16:50Z","timestamp":1732173410000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/iub.2918"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":59,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/iub.2918"],"URL":"https:\/\/doi.org\/10.1002\/iub.2918","archive":["Portico"],"relation":{},"ISSN":["1521-6543","1521-6551"],"issn-type":[{"value":"1521-6543","type":"print"},{"value":"1521-6551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"2024-06-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}