{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:06:28Z","timestamp":1789607188665,"version":"build-2803163510"},"reference-count":15,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,3,17]],"date-time":"2017-03-17T00:00:00Z","timestamp":1489708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004726","name":"Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004726","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:p>Mutations in <jats:italic><jats:styled-content style=\"fixed-case\">KARS<\/jats:styled-content><\/jats:italic>, which encodes for both mitochondrial and cytoplasmic lysyl\u2010<jats:styled-content style=\"fixed-case\">tRNA<\/jats:styled-content> synthetase, have been so far associated with three different phenotypes: the recessive form of Charcot\u2013Mary\u2013Tooth polyneuropathy, the autosomal recessive nonsyndromic hearing loss and the last recently described condition related to congenital visual impairment and progressive microcephaly. Here we report the case of a 14\u2010year\u2010old girl with severe cardiomyopathy associated to mild psychomotor delay and mild myopathy; moreover, a diffuse reduction of cytochrome C oxidase (<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>, complex <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content>) and a combined enzymatic defect of complex I (<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>) and complex <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">CIV<\/jats:styled-content>) was evident in muscle biopsy. Using the <jats:styled-content style=\"fixed-case\">TruSight<\/jats:styled-content> One sequencing panel we identified two novel mutations in <jats:italic><jats:styled-content style=\"fixed-case\">KARS<\/jats:styled-content><\/jats:italic>. Both mutations, never reported previously, occur in a highly conserved region of the catalytic domain and displayed a dramatic effect on <jats:styled-content style=\"fixed-case\">KARS<\/jats:styled-content> stability. Structural analysis confirmed the pathogenic role of the identified variants. Our findings confirm and emphasize that mt\u2010aminoacyl\u2010tRNA synthetases (mt\u2010<jats:styled-content style=\"fixed-case\">ARSs<\/jats:styled-content>) enzymes are related to a broad clinical spectrum due to their multiple and still unknown functions.<\/jats:p>","DOI":"10.1111\/cge.12931","type":"journal-article","created":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T05:32:42Z","timestamp":1480311162000},"page":"918-923","source":"Crossref","is-referenced-by-count":34,"title":["Novel mutations in <i><scp>KARS<\/scp><\/i> cause hypertrophic cardiomyopathy and combined mitochondrial respiratory chain defect"],"prefix":"10.1111","volume":"91","author":[{"given":"D.","family":"Verrigni","sequence":"first","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders Laboratory of Molecular Medicine  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Diodato","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders Laboratory of Molecular Medicine  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Di Nottia","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders Laboratory of Molecular Medicine  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Torraco","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders Laboratory of Molecular Medicine  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Bellacchio","sequence":"additional","affiliation":[{"name":"Research Laboratories \u2018Bambino Ges\u00f9\u2019 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Rizza","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders Laboratory of Molecular Medicine  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Tozzi","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders Laboratory of Molecular Medicine  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Verardo","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders Laboratory of Molecular Medicine  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Piemonte","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders Laboratory of Molecular Medicine  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Tasca","sequence":"additional","affiliation":[{"name":"Institute of Neurology Policlinico \u2018A. Gemelli\u2019 Foundation University Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"D'Amico","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders Laboratory of Molecular Medicine  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Bertini","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders Laboratory of Molecular Medicine  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Carrozzo","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders Laboratory of Molecular Medicine  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.69.1.617"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/787956"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.9.081307.164204"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.09.008"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.05.018"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073814553272"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005679"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2004.09.006"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006265200"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712072105"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01342"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.01.010"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/128_2013_457"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.04.006"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2012.07.027"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12931","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12931","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T07:07:19Z","timestamp":1696316839000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.12931"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,17]]},"references-count":15,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["10.1111\/cge.12931"],"URL":"https:\/\/doi.org\/10.1111\/cge.12931","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,17]]}}}