{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:10:03Z","timestamp":1768561803224,"version":"3.49.0"},"reference-count":8,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM136441"],"award-info":[{"award-number":["GM136441"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Pathogenic variants in the <jats:italic>NARS1<\/jats:italic> gene, which encodes for the asparaginyl\u2010tRNA synthetase1 (NARS1) enzyme, were associated with complex central and peripheral nervous system phenotypes. Recently, Charcot\u2013Marie\u2013Tooth (CMT) disease has been linked to heterozygous pathogenic variants in <jats:italic>NARS1<\/jats:italic> in nine patients. Here, we report two brothers and their mother from a French family with distal hereditary motor neuropathy (dHMN) carrying a previously unreported <jats:italic>NARS1<\/jats:italic> variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The <jats:italic>NARS1<\/jats:italic> variant (c.1555G&gt;C; p.(Gly519Arg)) was identified through whole\u2010genome sequencing (WGS) performed on the family members. Clinical findings, nerve conduction studies (NCS), needle electromyography (EMG), and functional assays in yeast complementation assays are reported here.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The family members showed symptoms of dHMN, including distal weakness and osteoarticular deformities. They also exhibited brisk reflexes suggestive of upper motor neuron involvement. All patients were able to walk independently at the last follow\u2010up. NCS and EMG confirmed pure motor neuropathy. Functional assays in yeast confirmed a loss\u2010of\u2010function effect of the variant on NARS1 activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our findings expand the clinical spectrum of <jats:italic>NARS1<\/jats:italic>\u2010associated neuropathies, highlighting the association of <jats:italic>NARS1<\/jats:italic> mutations with dHMN. The benign disease course observed in our patients suggests a slowly progressive phenotype. Further reports could contribute to a more comprehensive understanding of the spectrum of NARS1\u2010associated neuropathies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jns.12635","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T01:19:42Z","timestamp":1716254382000},"page":"275-278","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A previously unreported <i>NARS1<\/i> variant causes dominant distal hereditary motor neuropathy in a French family"],"prefix":"10.1111","volume":"29","author":[{"given":"Julian","family":"Theuriet","sequence":"first","affiliation":[{"name":"Service d'ENMG et de pathologies neuromusculaires, centre de r\u00e9f\u00e9rence des maladies neuromusculaires PACA\u2010R\u00e9union\u2010Rh\u00f4ne\u2010Alpes H\u00f4pital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Groupement Est  Bron France"},{"name":"Pathophysiology and Genetics of Neuron and Muscle CNRS UMR 5261, INSERM U1315, Universit\u00e9 Lyon 1, Facult\u00e9 de M\u00e9decine Lyon Est  Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheila","family":"Marte","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University of Michigan Medical School  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnaud","family":"Isapof","sequence":"additional","affiliation":[{"name":"Service de Neurologie P\u00e9diatrique H\u00f4pital Trousseau, Assistance Publique des H\u00f4pitaux de Paris  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alix","family":"de Becdeli\u00e8vre","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale H\u00f4pital Henri Mondor, Assistance Publique des H\u00f4pitaux de Paris  Cr\u00e9teil France"},{"name":"Laboratoire de biologie m\u00e9dicale multisites SeqOIA \u2013 PFMG2025  Paris 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France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcae070"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201017454\u20104"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.06.016"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx231"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddad054"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2016.11.013"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102011\u2010300952"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac453"}],"container-title":["Journal of the Peripheral Nervous 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