{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T20:24:39Z","timestamp":1785183879109,"version":"3.55.0"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/00619"],"award-info":[{"award-number":["PI20\/00619"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["S2017\/BMD3721"],"award-info":[{"award-number":["S2017\/BMD3721"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["00008286"],"award-info":[{"award-number":["00008286"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Regional Government of Madrid","award":["PI20\/00619"],"award-info":[{"award-number":["PI20\/00619"]}]},{"name":"Regional Government of Madrid","award":["S2017\/BMD3721"],"award-info":[{"award-number":["S2017\/BMD3721"]}]},{"name":"Regional Government of Madrid","award":["00008286"],"award-info":[{"award-number":["00008286"]}]},{"DOI":"10.13039\/501100009543","name":"Pontificia Universidad Javeriana of Bogot\u00e1","doi-asserted-by":"publisher","award":["PI20\/00619"],"award-info":[{"award-number":["PI20\/00619"]}],"id":[{"id":"10.13039\/501100009543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009543","name":"Pontificia Universidad Javeriana of Bogot\u00e1","doi-asserted-by":"publisher","award":["S2017\/BMD3721"],"award-info":[{"award-number":["S2017\/BMD3721"]}],"id":[{"id":"10.13039\/501100009543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009543","name":"Pontificia Universidad Javeriana of Bogot\u00e1","doi-asserted-by":"publisher","award":["00008286"],"award-info":[{"award-number":["00008286"]}],"id":[{"id":"10.13039\/501100009543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Dysfunction of some mitochondrial aminoacyl-tRNA synthetases (encoded by the KARS1, HARS2, LARS2 and NARS2 genes) results in a great variety of phenotypes ranging from non-syndromic hearing impairment (NSHI) to very complex syndromes, with a predominance of neurological signs. The diversity of roles that are played by these moonlighting enzymes and the fact that most pathogenic variants are missense and affect different domains of these proteins in diverse compound heterozygous combinations make it difficult to establish genotype\u2013phenotype correlations. We used a targeted gene-sequencing panel to investigate the presence of pathogenic variants in those four genes in cohorts of 175 Spanish and 18 Colombian familial cases with non-DFNB1 autosomal recessive NSHI. Disease-associated variants were found in five cases. Five mutations were novel as follows: c.766C&gt;T in KARS1, c.475C&gt;T, c.728A&gt;C and c.1012G&gt;A in HARS2, and c.795A&gt;G in LARS2. We provide audiograms from patients at different ages to document the evolution of the hearing loss, which is mostly prelingual and progresses from moderate\/severe to profound, the middle frequencies being more severely affected. No additional clinical sign was observed in any affected subject. Our results confirm the involvement of KARS1 in DFNB89 NSHI, for which until now there was limited evidence.<\/jats:p>","DOI":"10.3390\/genes15070951","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T15:47:32Z","timestamp":1721836052000},"page":"951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Novel Cases of Non-Syndromic Hearing Impairment Caused by Pathogenic Variants in Genes Encoding Mitochondrial Aminoacyl-tRNA Synthetases"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7583-0370","authenticated-orcid":false,"given":"Mar\u00eda","family":"Dom\u00ednguez-Ruiz","sequence":"first","affiliation":[{"name":"Servicio de Gen\u00e9tica, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Olarte","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Onecha","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica, Hospital Universitario Marqu\u00e9s de Valdecilla, IDIVAL, 39008 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3115-4910","authenticated-orcid":false,"given":"Irene","family":"Garc\u00eda-Vaquero","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"},{"name":"Programa de Doctorado en Biolog\u00eda, Escuela de Doctorado de la Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Gelvez","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greizy","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Villamar","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7985-592X","authenticated-orcid":false,"given":"Mat\u00edas","family":"Mor\u00edn","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3839-5098","authenticated-orcid":false,"given":"Miguel A.","family":"Moreno-Pelayo","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4268-2762","authenticated-orcid":false,"given":"Carmelo","family":"Morales-Angulo","sequence":"additional","affiliation":[{"name":"Servicio de Otorrinolaringolog\u00eda, Hospital Universitario Marqu\u00e9s de Valdecilla, IDIVAL, 39008 Santander, Spain"},{"name":"Facultad de Medicina, Universidad de Cantabria, 39005 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rub\u00e9n","family":"Polo","sequence":"additional","affiliation":[{"name":"Servicio de Otorrinolaringolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha L.","family":"Tamayo","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1188-3665","authenticated-orcid":false,"given":"Ignacio","family":"del Castillo","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1261\/rna.071720.119","article-title":"Aminoacyl-tRNA synthetases","volume":"26","author":"Ibba","year":"2020","journal-title":"RNA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e23219","DOI":"10.1096\/fj.202202024RR","article-title":"Aminoacyl-tRNA synthetase\u2014A molecular 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A"},{"key":"ref_37","first-page":"e1225","article-title":"Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy","volume":"92","author":"Bugiani","year":"2019","journal-title":"Neurology"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/7\/951\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:20:07Z","timestamp":1760109607000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/7\/951"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,19]]},"references-count":37,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["genes15070951"],"URL":"https:\/\/doi.org\/10.3390\/genes15070951","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,19]]}}}