Department of Pathology, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
Front Biosci (Schol Ed). 2024 Mar 14;16(1):7. doi: 10.31083/j.fbs1601007.
Disorders of mitochondrial function are responsible for many inherited neuromuscular and metabolic diseases. Their combination of high mortality, multi-systemic involvement, and economic burden cause devastating effects on patients and their families. Molecular diagnostic tools are becoming increasingly important in providing earlier diagnoses and guiding more precise therapeutic treatments for patients suffering from mitochondrial disorders. This review addresses fundamental molecular concepts relating to the pathogenesis of mitochondrial dysfunction and disorders. A series of short cases highlights the various clinical presentations, inheritance patterns, and pathogenic mutations in nuclear and mitochondrial genes that cause mitochondrial diseases. Graphical and tabular representations of the results are presented to guide the understanding of the important concepts related to mitochondrial molecular genetics and pathology. Emerging technology is incorporating preimplantation genetic testing for mtDNA disorders, while mitochondrial replacement shows promise in significantly decreasing the transfer of diseased mitochondrial DNA (mtDNA) to embryos. Medical professionals must maintain an in-depth understanding of the gene mutations and molecular mechanisms underlying mitochondrial disorders. Continued diagnostic advances and comprehensive management of patients with mitochondrial disorders are essential to achieve robust clinical impacts from comprehensive genomic testing. This is especially true when supported by non-genetic tests such as biochemical analysis, histochemical stains, and imaging studies. Such a multi-pronged investigation should improve the management of mitochondrial disorders by providing accurate and timely diagnoses to reduce disease burden and improve the lives of patients and their families.
线粒体功能障碍与许多遗传性神经肌肉和代谢疾病有关。这些疾病死亡率高、多系统受累且经济负担重，对患者及其家庭造成了毁灭性的影响。分子诊断工具在为线粒体功能障碍和疾病患者提供更早的诊断和更精确的治疗方面变得越来越重要。本综述介绍了与线粒体功能障碍和疾病发病机制相关的基本分子概念。一系列简短的病例强调了核基因和线粒体基因中导致线粒体疾病的各种临床表现、遗传模式和致病突变。以图表形式呈现结果，以帮助理解与线粒体分子遗传学和病理学相关的重要概念。新兴技术正在整合 mtDNA 疾病的植入前基因检测，而线粒体替换有望显著减少有缺陷的 mtDNA（mtDNA）向胚胎的转移。医疗专业人员必须深入了解线粒体疾病的基因突变和分子机制。不断推进诊断技术并全面管理线粒体疾病患者，对于从全面基因组检测中获得稳健的临床效果至关重要。当得到生化分析、组织化学染色和影像学研究等非遗传检测的支持时，这种多管齐下的研究方法应该可以改善线粒体疾病的管理，提供准确和及时的诊断，从而减轻疾病负担并改善患者及其家庭的生活。
