{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:44:28Z","timestamp":1760060668190,"version":"build-2065373602"},"reference-count":17,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["25-65-00031"],"award-info":[{"award-number":["25-65-00031"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: The COX20 gene encodes a critical assembly factor for cytochrome C oxidase (complex IV), and biallelic loss-of-function variants in this gene cause mitochondrial complex IV deficiency, typically presenting in infancy or childhood with hypotonia, ataxia, neuropathy, or dystonia. Methods: This study describes an adult male patient with a broad clinical spectrum of central and peripheral nervous system involvement. Different medical genetic tests were performed for the patient, and only whole-genome trio sequencing identified pathogenic variants in the COX20 gene. A review of previously reported cases was conducted to compare clinical and imaging findings. Results: Two compound heterozygous COX20 variants in were identified: a known missense variant (c.41A&gt;G; p.Lys14Arg) disrupting splicing, and a novel start-loss variant (c.2T&gt;C; p.Met1?). The patient exhibited progressive ataxia, pyramidal signs, and peripheral neuropathy, accompanied by cervical spinal cord atrophy on spinal cord MRI and lower leg muscle fat infiltration on muscle MRI, an imaging feature not previously emphasized in COX20-related disease. Conclusions: A review of previously reported cases underscores broad clinical variability of the COX20-associated disorder, which may contribute to a prolonged diagnostic odyssey.<\/jats:p>","DOI":"10.3390\/genes16091069","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T07:51:46Z","timestamp":1757577106000},"page":"1069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial Complex IV Deficiency Nuclear Type 11 Caused by a Novel Start-Lost Variant in the COX20 Gene"],"prefix":"10.3390","volume":"16","author":[{"given":"Anna","family":"Kuchina","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5871-8005","authenticated-orcid":false,"given":"Artem","family":"Borovikov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Sidorova","sequence":"additional","affiliation":[{"name":"Moscow Regional Research and Clinical Institute, 129110 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Orlova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1285-9093","authenticated-orcid":false,"given":"Oxana","family":"Ryzhkova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5462-2046","authenticated-orcid":false,"given":"Igor","family":"Zaigrin","sequence":"additional","affiliation":[{"name":"\u201cBiotech Campus\u201d LLC., 117437 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7023-7378","authenticated-orcid":false,"given":"Aysylu","family":"Murtazina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.semcdb.2017.08.055","article-title":"Mitochondrial Cytochrome c Oxidase Biogenesis: Recent Developments","volume":"76","author":"Abriata","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s00439-019-02026-4","article-title":"Observation of Novel COX20 Mutations Related to Autosomal Recessive Axonal Neuropathy and Static Encephalopathy","volume":"138","author":"Xu","year":"2019","journal-title":"Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1093\/brain\/awab135","article-title":"Bi-Allelic Loss of Function Variants in COX20 Gene Cause Autosomal Recessive Sensory Neuronopathy","volume":"144","author":"Dong","year":"2021","journal-title":"Brain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e125","DOI":"10.1093\/brain\/awac344","article-title":"The Phenotypic Spectrum of COX20-Associated Mitochondrial Disorder","volume":"145","author":"Ban","year":"2022","journal-title":"Brain"},{"doi-asserted-by":"crossref","unstructured":"Li, P., Guo, D., Zhang, X., Ji, K., Lv, H., Zhang, Y., Chen, Z., Ma, J., Fang, Y., and Liu, Y. (2022). Compound Heterozygous COX20 Variants Impair the Function of Mitochondrial Complex IV to Cause a Syndrome Involving Ophthalmoplegia and Visual Failure. Front. Neurol., 13.","key":"ref_5","DOI":"10.3389\/fneur.2022.873943"},{"doi-asserted-by":"crossref","unstructured":"Chen, L., and Liu, Y. (2023). Clinical and Genetic Characteristics of Children with COX20-Associated Mitochondrial Disorder: Case Report and Literature Review. BMC Med. Genomics, 16.","key":"ref_6","DOI":"10.1186\/s12920-023-01513-y"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1093\/hmg\/dds473","article-title":"A Mutation in the FAM36A Gene, the Human Ortholog of COX20, Impairs Cytochrome c Oxidase Assembly and Is Associated with Ataxia and Muscle Hypotonia","volume":"22","author":"Szklarczyk","year":"2013","journal-title":"Hum. Mol. 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