Abstract Leigh syndrome is an early onset progressive disorder caused by defects in mitochondrial oxidative phosphorylation. Pathogenic variants in nuclear and mitochondrial genes are associated with the syndrome. Homozygous pathogenic variants in the C12orf65 gene impair the mitochondrial oxidative phosphorylation system. We describe a new case of Leigh syndrome caused by a novel pathogenic variant of the C12orf65 gene resulting in the lack of the Gly-Gly-Gln (GGQ) domain in the predicted protein, and review clinical and molecular data from previously reported patients. Our study supports that the phenotype caused by C12orf65 gene variants is heterogeneous and varies from spastic paraparesis to Leigh syndrome. Loss-of-function variants are more likely to cause the disease, and variants affecting the GGQ domain tend to be associated with more severe phenotypes, reinforcing a possible genotype-phenotype correlation.

中文翻译：

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具有新型 C12orf65 致病性变异的患者的 Leigh 综合征：病例报告和文献复习

摘要 Leigh 综合征是一种由线粒体氧化磷酸化缺陷引起的早发性进行性疾病。核和线粒体基因的致病变异与该综合征有关。C12orf65 基因中的纯合致病变异损害线粒体氧化磷酸化系统。我们描述了一个由 C12orf65 基因的新型致病性变异引起的 Leigh 综合征新病例，该变异导致预测蛋白中缺少 Gly-Gly-Gln (GGQ) 结构域，并回顾了先前报告患者的临床和分子数据。我们的研究支持由 C12orf65 基因变异引起的表型是异质的，从痉挛性下肢轻瘫到 Leigh 综合征不等。功能丧失的变异更有可能导致这种疾病，