Abstract：
In this report, we discovered a new entity named cataract, alopecia, oral mucosal disorder, and psoriasis-like (CAOP) syndrome in two unrelated and ethnically diverse patients. Furthermore, patient 1 failed to respond to regular treatment. We found that CAOP syndrome was caused by an autosomal recessive defect in the mitochondrial membrane-bound transcription factor peptidase/site-1 protease (MBTPS1, 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 β-oxidation 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 MBTPS1 resulted in a new entity of CAOP syndrome and elucidated the mechanism of the mutations in the new disease.
摘要：
在这份报告中,我们发现了一个名为白内障的新实体，脱发,口腔粘膜疾病，和银屑病样（CAOP）综合征在两个无关和种族不同的患者。此外，患者1对常规治疗无效.我们发现CAOP综合征是由线粒体膜结合转录因子肽酶/位点1蛋白酶（MBTPS1，S1P）的常染色体隐性缺陷引起的。在患有CAOP综合征的患者1中观察到线粒体异常。此外，我们发现S1P是一种新型的线粒体蛋白，与ETFA/ETFB形成三聚体复合物。S1P可增强ETFA/ETFB的风味并保持其稳定性。患者S1P变体使ETFA/ETFB不稳定，损害线粒体呼吸，降低脂肪酸β-氧化活性，并将线粒体氧化磷酸化（OXPHOS）转移到糖酵解。补充核黄素可显著改善患者1的线粒体功能障碍和炎性病变，恢复了ETFA/ETFB的稳定性。我们的研究发现MBTPS1的突变导致CAOP综合征的新实体，并阐明了新疾病中突变的机制。
