{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:35:03Z","timestamp":1790692503855,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81671245"],"award-info":[{"award-number":["81671245"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004835","name":"Zhejiang University","doi-asserted-by":"publisher","award":["188020\u20131938"],"award-info":[{"award-number":["188020\u20131938"]}],"id":[{"id":"10.13039\/501100004835","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004835","name":"Zhejiang University","doi-asserted-by":"publisher","award":["10101\/089"],"award-info":[{"award-number":["10101\/089"]}],"id":[{"id":"10.13039\/501100004835","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2019XZZX001-01\u201304"],"award-info":[{"award-number":["2019XZZX001-01\u201304"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Sensory neuronopathies are a rare and distinct subgroup of peripheral neuropathies, characterized by degeneration of the dorsal root ganglia neurons. About 50% of sensory neuronopathies are idiopathic and genetic causes remain to be clarified. Through a combination of homozygosity mapping and whole exome sequencing, we linked an autosomal recessive sensory neuronopathy to pathogenic variants in the COX20 gene. We identified eight unrelated families from the eastern Chinese population carrying a founder variant c.41A&amp;gt;G (p.Lys14Arg) within COX20 in either a homozygous or compound heterozygous state. All patients displayed sensory ataxia with a decrease in non-length-dependent sensory potentials. COX20 encodes a key transmembrane protein implicated in the assembly of mitochondrial complex IV. We showed that COX20 variants lead to reduction of COX20 protein in patient\u2019s fibroblasts and transfected cell lines, consistent with a loss-of-function mechanism. Knockdown of COX20 expression in ND7\/23 sensory neuron cells resulted in complex IV deficiency and perturbed assembly of complex IV, which subsequently compromised cell spare respiratory capacity and reduced cell proliferation under metabolic stress. Consistent with mitochondrial dysfunction in knockdown cells, reduced complex IV assembly, enzyme activity and oxygen consumption rate were also found in patients\u2019 fibroblasts. We speculated that the mechanism of COX20 was similar to other causative genes (e.g. SURF1, COX6A1, COA3 and SCO2) for peripheral neuropathies, all of which are functionally important in the structure and assembly of complex IV. Our study identifies a novel causative gene for the autosomal recessive sensory neuronopathy, whose vital function in complex IV and high expression in the proprioceptive sensory neuron further underlines loss of COX20 contributing to mitochondrial bioenergetic dysfunction as a mechanism in peripheral sensory neuron disease.<\/jats:p>","DOI":"10.1093\/brain\/awab135","type":"journal-article","created":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T12:09:43Z","timestamp":1616242183000},"page":"2457-2470","source":"Crossref","is-referenced-by-count":29,"title":["Bi-allelic loss of function variants in <i>COX20<\/i> gene cause autosomal recessive sensory neuronopathy"],"prefix":"10.1093","volume":"144","author":[{"given":"Hai-Lin","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, 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Province, Zhejiang University School of Medicine, 310009, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Qi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, 310009, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gong-Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, 310009, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Fu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology and Research Center of Neurology in Second Affiliated 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and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, 310009, Hangzhou, China"},{"name":"NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2106-572X","authenticated-orcid":false,"given":"Zhi-Ying","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, 310009, Hangzhou, China"},{"name":"NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of 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