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Furthermore, patient 1 failed to respond to regular treatment. We found that\u00a0CAOP syndrome was caused by an autosomal recessive defect in the mitochondrial membrane\u2010bound transcription factor peptidase\/site\u20101 protease (\n                    <jats:italic>MBTPS1<\/jats:italic>\n                    , S1P). Mitochondrial abnormalities were observed in patient 1 with CAOP syndrome. Furthermore, we found that S1P is a novel mitochondrial protein that forms a trimeric complex with ETFA\/ETFB. S1P enhances ETFA\/ETFB flavination and maintains its stability. Patient S1P variants destabilize ETFA\/ETFB, impair mitochondrial respiration, decrease fatty acid \u03b2\u2010oxidation activity, and shift mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis. Mitochondrial dysfunction and inflammatory lesions in patient 1 were significantly ameliorated by riboflavin supplementation, which restored the stability of ETFA\/ETFB. Our study discovered that mutations in\n                    <jats:italic>MBTPS1<\/jats:italic>\n                    resulted in a new entity of CAOP syndrome and elucidated the mechanism of the mutations in the new disease.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202114904","type":"journal-article","created":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T04:05:41Z","timestamp":1648785941000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["S1P defects cause a new entity of cataract, alopecia, oral mucosal disorder, and psoriasis\u2010like syndrome"],"prefix":"10.1038","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7439-4845","authenticated-orcid":false,"given":"Fuying","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3490-6735","authenticated-orcid":false,"given":"Xiaoxiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruhong","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3378-4676","authenticated-orcid":false,"given":"Chaolan","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianying","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4344-5363","authenticated-orcid":false,"given":"Jinke","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4962-1396","authenticated-orcid":false,"given":"Y Eugene","family":"Chin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7785-7112","authenticated-orcid":false,"given":"Yi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"She","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Htun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin F","family":"Mathes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra G","family":"de Alba Campomanes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M","family":"Slavotinek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5682-4995","authenticated-orcid":false,"given":"Si","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3053-2756","authenticated-orcid":false,"given":"Ming","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0785-8985","authenticated-orcid":false,"given":"Zhirong","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,1]]},"reference":[{"key":"BFEMMM202114904_CR1","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1002\/jimd.12058","volume":"42","author":"S Balasubramaniam","year":"2019","unstructured":"Balasubramaniam S, Christodoulou J, Rahman S (2019) Disorders of riboflavin metabolism. 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