{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:17:49Z","timestamp":1785827869891,"version":"3.56.0"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,2,28]],"date-time":"2021-02-28T00:00:00Z","timestamp":1614470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Gr 970\/9\u20101"],"award-info":[{"award-number":["Gr 970\/9\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010564","name":"Deutsche Zentrum f\u00fcr Lungenforschung","doi-asserted-by":"publisher","award":["FKZ 82DZL23A2"],"award-info":[{"award-number":["FKZ 82DZL23A2"]}],"id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000921","name":"European Cooperation in Science and Technology","doi-asserted-by":"publisher","award":["CA 16125 ENTeR\u2010chILD"],"award-info":[{"award-number":["CA 16125 ENTeR\u2010chILD"]}],"id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004410","name":"European Molecular Biology Organization","doi-asserted-by":"publisher","award":["ALTF 243\u20102018"],"award-info":[{"award-number":["ALTF 243\u20102018"]}],"id":[{"id":"10.13039\/100004410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001656","name":"Helmholtz-Gemeinschaft","doi-asserted-by":"publisher","award":["ZT\u2010I\u20100003"],"award-info":[{"award-number":["ZT\u2010I\u20100003"]}],"id":[{"id":"10.13039\/501100001656","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010564","name":"Deutsche Zentrum f\u00fcr Lungenforschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Aminoacyl\u2010tRNA synthetases (ARSs) catalyze the first step of protein biosynthesis (canonical function) and have additional (non\u2010canonical) functions outside of translation. Bi\u2010allelic pathogenic variants in genes encoding ARSs are associated with various recessive mitochondrial and multisystem disorders. We describe here a multisystem clinical phenotype based on bi\u2010allelic mutations in the two genes (\n                    <jats:italic>FARSA, FARSB<\/jats:italic>\n                    ) encoding distinct subunits for tetrameric cytosolic phenylalanyl\u2010tRNA synthetase (FARS1). Interstitial lung disease with cholesterol pneumonitis on histology emerged as an early characteristic feature and significantly determined disease burden. Additional clinical characteristics of the patients included neurological findings, liver dysfunction, and connective tissue, muscular and vascular abnormalities. Structural modeling of newly identified missense mutations in the alpha subunit of FARS1,\n                    <jats:italic>FARSA<\/jats:italic>\n                    , showed exclusive mapping to the enzyme's conserved catalytic domain. Patient\u2010derived mutant cells displayed compromised aminoacylation activity in two cases, while remaining unaffected in another. Collectively, these findings expand current knowledge about the human ARS disease spectrum and support a loss of canonical and non\u2010canonical function in FARS1\u2010associated recessive disease.\n                  <\/jats:p>","DOI":"10.1111\/cge.13943","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T11:39:40Z","timestamp":1613821180000},"page":"789-801","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["<scp>FARS1<\/scp>\n                    \u2010related disorders caused by bi\u2010allelic mutations in cytosolic phenylalanyl\u2010\n                    <scp>tRNA<\/scp>\n                    synthetase genes: Look beyond the lungs!"],"prefix":"10.1111","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7445-4895","authenticated-orcid":false,"given":"Luise A.","family":"Schuch","sequence":"first","affiliation":[{"name":"Department of Pediatrics Dr. von Hauner Children's Hospital, LMU Munich  Munich Germany"},{"name":"German Center for Lung Research (DZL)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1468-6969","authenticated-orcid":false,"given":"Maria","family":"Forstner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Dr. von Hauner Children's Hospital, LMU Munich  Munich Germany"},{"name":"German Center for Lung Research (DZL)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7371-8158","authenticated-orcid":false,"given":"Christina K.","family":"Rapp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Dr. von Hauner Children's Hospital, LMU Munich  Munich Germany"},{"name":"German Center for Lung Research (DZL)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8123-0876","authenticated-orcid":false,"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Dr. von Hauner Children's Hospital, LMU Munich  Munich Germany"},{"name":"German Center for Lung Research (DZL)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2053-3392","authenticated-orcid":false,"given":"Desiree E. C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Metabolic Unit, Department of Clinical Chemistry Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam The Netherlands"},{"name":"Amsterdam Gastroenterology &amp; Metabolism Amsterdam Neuroscience  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6617-3698","authenticated-orcid":false,"given":"Marisa I.","family":"Mendes","sequence":"additional","affiliation":[{"name":"Metabolic Unit, Department of Clinical Chemistry Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam The Netherlands"},{"name":"Amsterdam Gastroenterology &amp; Metabolism Amsterdam Neuroscience  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7021-087X","authenticated-orcid":false,"given":"Florent","family":"Delhommel","sequence":"additional","affiliation":[{"name":"Institute of Structural Biology Helmholtz Zentrum M\u00fcnchen  Neuherberg Germany"},{"name":"Center for Integrated Protein Science Munich, Department of Chemistry Technical University of Munich  Garching Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1594-0527","authenticated-orcid":false,"given":"Michael","family":"Sattler","sequence":"additional","affiliation":[{"name":"Institute of Structural Biology Helmholtz Zentrum M\u00fcnchen  Neuherberg Germany"},{"name":"Center for Integrated Protein Science Munich, Department of Chemistry Technical University of Munich  Garching Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1405-8401","authenticated-orcid":false,"given":"Nagehan","family":"Emiralio\u011flu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology, Faculty of Medicine Hacettepe University  Ankara 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