Mitochondrial disorders are one of the most common inherited metabolic disorders and are caused by variants in nuclear genes or the mitochondrial genome. Additionally, there is a large group of patients displaying clinical symptoms, where the genetic background is unknown. Mitochondrial disorders have a huge variety in their clinical presentation, making diagnostics challenging. Genomes of higher organisms contain around 95% non-protein-coding DNA. Recently, non-protein-coding sequences have been shown to affect gene expression in many cellular processes, including mitochondrial functioning. As these insights are not frequently incorporated in diagnostics we propose a workflow utilizing this knowledge for faster diagnostics of patients lacking a molecular diagnosis.

中文翻译：

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非编码基因组变异引起的线粒体功能障碍——改进诊断的建议工作流程

线粒体疾病是最常见的遗传性代谢疾病之一，由核基因或线粒体基因组的变异引起。此外，还有一大群患者表现出临床症状，其中遗传背景未知。线粒体疾病的临床表现多种多样，使诊断具有挑战性。高等生物的基因组包含大约 95% 的非蛋白质编码 DNA。最近，非蛋白质编码序列已被证明会影响许多细胞过程中的基因表达，包括线粒体功能。由于这些见解并不经常被纳入诊断，我们提出了一个工作流程，利用这些知识对缺乏分子诊断的患者进行更快的诊断。