Mitochondrial diseases: expanding the diagnosis in the era of genetic testing.

Mitochondrial diseases are clinically and genetically heterogeneous. These diseases were initially described a little over three decades ago. Limited diagnostic tools created disease descriptions based on clinical, biochemical analytes, neuroimaging, and muscle biopsy findings. This diagnostic mechanism continued to evolve detection of inherited oxidative phosphorylation disorders and expanded discovery of mitochondrial physiology over the next two decades. Limited genetic testing hampered the definitive diagnostic identification and breadth of diseases. Over the last decade, the development and incorporation of massive parallel sequencing has identified approximately 300 genes involved in mitochondrial disease. Gene testing has enlarged our understanding of how genetic defects lead to cellular dysfunction and disease. These findings have expanded the understanding of how mechanisms of mitochondrial physiology can induce dysfunction and disease, but the complete collection of disease-causing gene variants remains incomplete. This article reviews the developments in disease gene discovery and the incorporation of gene findings with mitochondrial physiology. This understanding is critical to the development of targeted therapies.

线粒体疾病在临床和遗传方面具有异质性。这些疾病在三十多年前首次被描述。有限的诊断工具根据临床、生化分析物、神经影像学和肌肉活检结果来描述疾病。在接下来的二十年里，这种诊断机制不断发展，用于检测遗传性氧化磷酸化障碍，并扩大了对线粒体生理学的发现。有限的基因检测阻碍了疾病的确切诊断识别和疾病种类的涵盖范围。在过去的十年中，大规模平行测序技术的发展和应用已经确定了大约300个与线粒体疾病有关的基因。基因检测扩大了我们对基因缺陷如何导致细胞功能障碍和疾病的理解。这些发现拓宽了对线粒体生理机制如何引发功能障碍和疾病的认识，但致病基因变异的完整集合仍然不完整。本文综述了疾病基因发现的进展以及基因发现与线粒体生理学的结合。这种理解对靶向治疗的发展至关重要。