{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:18:34Z","timestamp":1787804314124,"version":"build-2784847793"},"reference-count":15,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>COX14<\/jats:italic>\n                    encodes a transmembrane protein essential for cytochrome c oxidase (COX) complex assembly. A homozygous missense variant in\n                    <jats:italic>COX14<\/jats:italic>\n                    was reported in three siblings from a single consanguineous family with severe, fatal infantile mitochondrial complex IV deficiency nuclear type 10 (MC4DN10; MIM# 619053). No additional cases have been identified since, and the ClinGen Mitochondrial Disease Gene Curation Expert Panel classified the\n                    <jats:italic>COX14<\/jats:italic>\n                    \u2013MC4DN10 gene\u2013disease association as having limited evidence. We report a 9\u2010year\u2010old male with biallelic\n                    <jats:italic>COX14<\/jats:italic>\n                    variants (c.82delT, p.Tyr28Thrfs*83, and c.3G&gt;A, p.Met1?) representing the second unrelated family with MC4DN10. In contrast to the fatal neonatal course previously described, this individual demonstrates an attenuated encephalomyopathic phenotype with prolonged survival. Initial presentation at 6\u2009months included hypotonia, feeding difficulties, and developmental delay. Previously unreported features included growth hormone deficiency, ascending aortic dilation, and distinct neuroradiological findings. At age 8\u2009years, he developed neurological regression and ataxia with brain MRI findings consistent with Leigh syndrome. Muscle biopsy confirmed reduced COX enzymatic activity (33% of mean). Identification of a second unrelated family with biallelic\n                    <jats:italic>COX14<\/jats:italic>\n                    variants and biochemically confirmed complex IV deficiency strengthens the gene\u2013disease association for MC4DN10. This individual presents an attenuated encephalomyopathic phenotype with novel endocrine and cardiovascular manifestations, underscoring the importance of genomic evaluation in suspected mitochondrial disorders even in the absence of classic biochemical markers such as lactic acidosis.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70260","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T03:34:11Z","timestamp":1787801651000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>\n                      <i>COX14<\/i>\n                    <\/scp>\n                    Variants Are Associated With Mitochondrial Complex\n                    <scp>IV<\/scp>\n                    Deficiency Nuclear Type 10 (\n                    <scp>MC4DN10<\/scp>\n                    )"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2288-3572","authenticated-orcid":false,"given":"Elias K.","family":"Awad","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4120-6828","authenticated-orcid":false,"given":"Emily","family":"Waskow","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Children's Hospital of San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hari","family":"Tunuguntla","sequence":"additional","affiliation":[{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Pediatrics, Section of Pediatric Cardiology Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9539-6252","authenticated-orcid":false,"given":"Joseph","family":"Spinner","sequence":"additional","affiliation":[{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Pediatrics, Section of Pediatric Cardiology Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2348-9262","authenticated-orcid":false,"given":"Hanna J.","family":"Tadros","sequence":"additional","affiliation":[{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Pediatrics, Section of Pediatric Cardiology Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa T.","family":"Emrick","sequence":"additional","affiliation":[{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Section of Pediatric Neurology and Developmental Neurosciences, Department of Pediatrics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6860-372X","authenticated-orcid":false,"given":"Daniel G.","family":"Calame","sequence":"additional","affiliation":[{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Section of Pediatric Neurology and Developmental Neurosciences, Department of Pediatrics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3502-8460","authenticated-orcid":false,"given":"Fernando","family":"Scaglia","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Joint BCM\u2010CUHK Center of Medical Genetics Prince of Wales Hospital  Hong Kong SAR China"},{"name":"Baylor Genetics  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102013\u2010102256"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.02.007"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1161\/CIRCRESAHA.107.162800","article-title":"Molecular mechanisms of angiotensin II mediated mitochondrial dysfunction: linking mitochondrial oxidative damage and vascular endothelial dysfunction","volume":"102","author":"Doughan A. 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