{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T11:04:45Z","timestamp":1784631885263,"version":"3.55.0"},"reference-count":12,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T00:00:00Z","timestamp":1646784000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF\u20102016\u201002361241"],"award-info":[{"award-number":["RF\u20102016\u201002361241"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009886","name":"Regione Puglia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009886","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Genetic defect in the nuclear encoded subunits of cytochrome <jats:italic>c<\/jats:italic> oxidase are very rare. To date, most deleterious variants affect the mitochondrially encoded subunits of complex IV and the nuclear genes encoded for assembly factors. A biallelic pathogenic variant in the mitochondrial complex IV subunit COX5A was previously reported in a couple of sibs with failure to thrive, lactic acidosis and pulmonary hypertension and a lethal phenotype. Here, we describe a second family with a 11\u2010year\u2010old girl presenting with failure to thrive, lactic acidosis, hypoglycemia and short stature. Clinical exome revealed the homozygous missense variant c.266\u2009T\u2009&gt;\u2009G in COX5A, which produces a drop of the corresponding protein and a reduction of the COX activity. Compared to the previous observation, this girl showed an attenuated metabolic derangement without involvement of the cardiovascular system and neurodevelopment. Our observation confirms that COX5A recessive variants may cause mitochondrial disease and expands the associated phenotype to less severe presentations.<\/jats:p>","DOI":"10.1111\/cge.14127","type":"journal-article","created":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T05:01:02Z","timestamp":1646456462000},"page":"56-60","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A novel homozygous variant in <scp><i>COX5A<\/i><\/scp> causes an attenuated phenotype with failure to thrive, lactic acidosis, hypoglycemia, and short stature"],"prefix":"10.1111","volume":"102","author":[{"given":"Alessandra","family":"Torraco","sequence":"first","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Morlino","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Fondazione IRCCS\u2010Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Rizza","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Di Nottia","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Bottaro","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Pediatric University Department Bambino Ges\u00f9 Children's Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Bisceglia","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Fondazione IRCCS\u2010Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Montanari","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnologies \u201cC. Darwin\u201d Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Cappa","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Pediatric University Department Bambino Ges\u00f9 Children's Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6069-0993","authenticated-orcid":false,"given":"Marco","family":"Castori","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Fondazione IRCCS\u2010Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Bertini","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3327-4054","authenticated-orcid":false,"given":"Rosalba","family":"Carrozzo","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/1534056"},{"key":"e_1_2_9_3_1","first-page":"163","article-title":"Mitochondrial cytochrome c oxidase biogenesis: recent developments","volume":"76","author":"Tim\u00f3n\u2010G\u00f3mez A","year":"2018","journal-title":"Cell Dev Biol"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019103912"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23210"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.11.2017"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24195"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.1150181131"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019102817"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.151"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.930000.55.S2.27"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20091714"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-018-0172-z"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14127","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.14127","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T20:21:02Z","timestamp":1692822062000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,9]]},"references-count":12,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1111\/cge.14127"],"URL":"https:\/\/doi.org\/10.1111\/cge.14127","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,9]]},"assertion":[{"value":"2022-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}