Complex III (CIII) is the third out of five mitochondrial respiratory chain complexes residing at the mitochondrial inner membrane. The assembly of 10 subunits encoded by nuclear DNA and one by mitochondrial DNA result in the functional CIII which transfers electrons from ubiquinol to cytochrome c. Deficiencies of CIII are among the least investigated mitochondrial disorders and thus clinical spectrum of patients with mutations in CIII is not well defined. We report on a 10-year-old girl born to consanguineous Iranian parents presenting with recurrent visual loss episodes and optic nerve contrast enhancement in brain imaging reminiscent of an acquired demyelination syndrome (i.e. optic neuritis or multiple sclerosis), who was ultimately confirmed to have a novel homozygous missense variant of unknown significance, c.949C > T; p.(Arg317Trp) in the CYC1 gene, a nuclear DNA subunit of complex III of the mitochondrial chain. Sanger sequencing confirmed the segregation of this variant with disease in the family. The effect of this variant on the protein structure was shown in-silico. Our findings, not only expand the clinical spectrum due to defects in CYC1 gene but also highlight that mitochondrial respiratory chain disorders could be considered as a potential differential diagnosis in children who present with unusual patterns of acquired demyelination syndromes (ADS). In addition, our results support the hypothesis that mitochondrial disorders might have an overlapping presentation with ADS.

复合物 III (CIII) 是位于线粒体内膜的五个线粒体呼吸链复合物中的第三个。由核 DNA 编码的 10 个亚基和由线粒体 DNA 编码的 1 个亚基的组装产生了功能性 CIII，它将电子从泛醇转移到细胞色素c. CIII 缺陷是研究最少的线粒体疾病之一，因此 CIII 突变患者的临床谱尚不明确。我们报告了一名伊朗近亲父母所生的 10 岁女孩，她出现反复的视力丧失发作和脑成像中的视神经对比增强，让人联想到获得性脱髓鞘综合征（即视神经炎或多发性硬化症），最终被证实患有一种意义不明的新型纯合错义变体，c.949C > T；p.(Arg317Trp) 在CYC1基因中，这是线粒体链复合物 III 的核 DNA 亚基。Sanger测序证实了这种变异与家族疾病的分离。该变体对蛋白质结构的影响在计算机上显示. 我们的研究结果不仅扩大了由于CYC1基因缺陷导致的临床范围，而且还强调了线粒体呼吸链疾病可被视为具有不寻常的获得性脱髓鞘综合征 (ADS) 模式的儿童的潜在鉴别诊断。此外，我们的结果支持线粒体疾病可能与 ADS 有重叠表现的假设。