{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:03:43Z","timestamp":1790071423275,"version":"4.0.1"},"reference-count":7,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"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":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2026,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background and Aims<\/jats:title>\n \n SCO2<\/jats:italic>\n encodes a mitochondrial copper chaperone required for cytochrome c oxidase (COX) assembly and is classically associated with severe multisystem mitochondrial disease. We characterize a motor\u2010predominant axonal neuropathy presentation associated with biallelic SCO2 variants.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Clinical, genetic, and functional studies were performed in a 15\u2010year\u2010old female presenting with axonal neuropathy. Functional studies were conducted in patient\u2010derived fibroblasts, including Western blot analysis and spectrophotometric cytochrome c oxidation assay. Structural modeling was performed using ChimeraX.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The patient presented with a motor\u2010predominant axonal neuropathy consistent with Charcot\u2010Marie\u2010Tooth (CMT) disease. Clinical genetic testing identified compound heterozygous\n SCO2<\/jats:italic>\n variants of uncertain significance: a missense variant (p.Arg120Trp) and a frameshift variant (p.Asp252ValfsTer24). Structural modeling predicted disruption of protein stability for both variants. Functional studies in patient\u2010derived fibroblasts demonstrated complete absence of SCO2 protein and reduced mitochondrial complex IV activity, supporting a loss\u2010of\u2010function mechanism.\n <\/jats:p>\n <\/jats:sec>\n \n Interpretation<\/jats:title>\n \n These findings demonstrate that\n SCO2<\/jats:italic>\n \u2010related disease can present as an isolated axonal neuropathy, a phenotype that remains rarely reported. Our study also highlights the value of integrating in silico prediction tools with functional assays to establish pathogenicity in rare sporadic cases of inherited neuropathy.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jns.70150","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T02:03:06Z","timestamp":1784858586000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biallelic\n SCO2<\/i>\n Variants Presenting as Motor\u2010Predominant Axonal Neuropathy With Complex\n IV<\/scp>\n Deficiency"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5669-7415","authenticated-orcid":false,"given":"Adriana P.","family":"Rebelo","sequence":"first","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics University of Miami Miller School of Medicine Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Lutz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The University of Iowa Roy J and Lucille A Carver College of Medicine Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2236-9218","authenticated-orcid":false,"given":"Tiffany","family":"Grider","sequence":"additional","affiliation":[{"name":"Neurology The University of Iowa Roy J and Lucille A Carver College of Medicine Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig M.","family":"Zaidman","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University in St. Louis St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8460-6971","authenticated-orcid":false,"given":"Michael E.","family":"Shy","sequence":"additional","affiliation":[{"name":"Neurology The University of Iowa Roy J and Lucille A Carver College of Medicine Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Zuchner","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics University of Miami Miller School of Medicine Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506801200"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/15513"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.57.8.1440"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000630"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx369"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24338"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad158"}],"container-title":["Journal of the Peripheral Nervous System"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jns.70150","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jns.70150","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jns.70150","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:14:30Z","timestamp":1790068470000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jns.70150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":7,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/jns.70150"],"URL":"https:\/\/doi.org\/10.1111\/jns.70150","archive":["Portico"],"relation":{},"ISSN":["1085-9489","1529-8027"],"issn-type":[{"value":"1085-9489","type":"print"},{"value":"1529-8027","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]},"assertion":[{"value":"2026-05-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70150"}}