{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:58:16Z","timestamp":1787497096292,"version":"build-2736575974"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"2","funder":[{"name":"Humboldt Research Fellowship Programme"},{"name":"Michigan Pre-doctoral Training Program in Genetics","award":["GM007544"],"award-info":[{"award-number":["GM007544"]}]},{"name":"National Research Service Award"},{"name":"National Institute of Neurological Diseases and Stroke","award":["NS108510"],"award-info":[{"award-number":["NS108510"]}]},{"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"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R24NS098523"],"award-info":[{"award-number":["R24NS098523"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R37NS054154"],"award-info":[{"award-number":["R37NS054154"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002721","name":"Charcot-Marie-Tooth","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002721","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5U54NS065712"],"award-info":[{"award-number":["5U54NS065712"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01NS105755"],"award-info":[{"award-number":["5R01NS105755"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union's Horizon 2020","award":["779257"],"award-info":[{"award-number":["779257"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pathogenic variants in six aminoacyl-tRNA synthetase (ARS) genes are implicated in neurological disorders, most notably inherited peripheral neuropathies. ARSs are enzymes that charge tRNA molecules with cognate amino acids. Pathogenic variants in asparaginyl-tRNA synthetase (NARS1) cause a neurological phenotype combining developmental delay, ataxia and demyelinating peripheral neuropathy. NARS1 has not yet been linked to axonal Charcot\u2013Marie\u2013Tooth disease. Exome sequencing of patients with inherited peripheral neuropathies revealed three previously unreported heterozygous NARS1 variants in three families. Clinical and electrophysiological details were assessed. We further characterized all three variants in a yeast complementation model and used a knock-in mouse model to study variant p.Ser461Phe. All three variants (p.Met236del, p.Cys342Tyr and p.Ser461Phe) co-segregate with the sensorimotor axonal neuropathy phenotype. Yeast complementation assays show that none of the three NARS1 variants support wild-type yeast growth when tested in isolation (i.e. in the absence of a wild-type copy of NARS1), consistent with a loss-of-function effect. Similarly, the homozygous knock-in mouse model (p.Ser461Phe\/Ser472Phe in mouse) also demonstrated loss-of-function characteristics. We present three previously unreported NARS1 variants segregating with a sensorimotor neuropathy phenotype in three families. Functional studies in yeast and mouse support variant pathogenicity. Thus, NARS1 is the seventh ARS implicated in dominant axonal Charcot\u2013Marie\u2013Tooth disease, further stressing that all dimeric ARSs should be evaluated for Charcot\u2013Marie\u2013Tooth disease.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae070","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T17:59:06Z","timestamp":1709747946000},"source":"Crossref","is-referenced-by-count":19,"title":["Dominant\n                    <i>NARS1<\/i>\n                    mutations causing axonal Charcot\u2013Marie\u2013Tooth disease expand\n                    <i>NARS1<\/i>\n                    -associated diseases"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6593-7644","authenticated-orcid":false,"given":"Danique","family":"Beijer","sequence":"first","affiliation":[{"name":"Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp , Wilrijk, B-2610 , Belgium"},{"name":"Laboratory of Neuromuscular Pathology, Institute Born-Bunge, University of Antwerp , Wilrijk, B-2610 , Belgium"},{"name":"Department for Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami , Miami, FL 33136 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Marte","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Michigan Medical School , Ann Arbor, MI 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin C","family":"Li","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609 , USA"},{"name":"Genetics Program, Graduate School of Biomedical Sciences, Tufts University , Boston, MA 02111 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem","family":"De Ridder","sequence":"additional","affiliation":[{"name":"Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp , Wilrijk, B-2610 , Belgium"},{"name":"Laboratory of Neuromuscular Pathology, Institute Born-Bunge, University of Antwerp , Wilrijk, B-2610 , Belgium"},{"name":"Neuromuscular Reference Centre, Department of Neurology, Antwerp University Hospital , Wilrijk, B-2610 , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie Z","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Austin Health , Melbourne, VIC 3084 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail L D","family":"Tadenev","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy E","family":"Miers","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tine","family":"Deconinck","sequence":"additional","affiliation":[{"name":"Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp , Wilrijk, B-2610 , Belgium"},{"name":"Center of Medical Genetics, University of Antwerp and Antwerp University Hospital , Edegem, B-2650 , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Macdonell","sequence":"additional","affiliation":[{"name":"Department of Neurology, Austin Health , Melbourne, VIC 3084 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Wilson","family":"Marques","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Behavior Sciences, School of Medicine of Ribeir\u00e3o Preto, University of S\u00e3o Paulo , S\u00e3o Paulo, SP, 14051-140 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"De Jonghe","sequence":"additional","affiliation":[{"name":"Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp , Wilrijk, B-2610 , Belgium"},{"name":"Laboratory of Neuromuscular Pathology, Institute Born-Bunge, University of Antwerp , Wilrijk, B-2610 , Belgium"},{"name":"Neuromuscular Reference Centre, Department of Neurology, Antwerp University Hospital , Wilrijk, B-2610 , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia L","family":"Pratt","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609 , USA"},{"name":"Neuroscience Program, Graduate School of Biomedical Sciences, Tufts University , Boston, MA 02111 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Meyer-Schuman","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8498-5235","authenticated-orcid":false,"given":"Stephan","family":"Z\u00fcchner","sequence":"additional","affiliation":[{"name":"Department for Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami , Miami, FL 33136 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5820-3156","authenticated-orcid":false,"given":"Anthony","family":"Antonellis","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Michigan Medical School , Ann Arbor, MI 48109 , USA"},{"name":"Department of Neurology, University of Michigan Medical School , Ann Arbor, MI 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9229-3407","authenticated-orcid":false,"given":"Robert W","family":"Burgess","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609 , USA"},{"name":"Genetics Program, Graduate School of Biomedical Sciences, Tufts University , Boston, MA 02111 , USA"},{"name":"Neuroscience Program, Graduate School of Biomedical Sciences, Tufts University , Boston, MA 02111 , 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