Université de Paris et Service de Génétique Moléculaire, Reference Center for Mitochondrial Diseases (CARAMMEL), Groupe Hospitalier Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris , Paris, France.
Laboratory for Genetics of Mitochondrial Disorders, INSERM U1163, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine , Paris, France.
Expert Rev Mol Diagn. 2020 Oct;20(10):1003-1008. doi: 10.1080/14737159.2020.1820326. Epub 2020 Sep 20.
Currently, genetic testing of mitochondrial DNA mutations includes screening for single-nucleotide variants, several base pair insertions or deletions, large-scale deletions, or relative depletion of total mitochondrial DNA content. Within the last decade, next-generation sequencing (NGS) has resulted in remarkable advances in the field of mitochondrial diseases (MD) and has become a routine step of the diagnostic workup.
We aimed to present an overview of current technologies employed in molecular diagnosis of mitochondrial DNA diseases. We report on the recent contributions of NGS testing to the diagnosis and understanding of MD.
The progress of NGS technologies allows the simultaneous detection of mutations and quantification of the heteroplasmy level, ensuring sensitivity and specificity requested for the detection of mitochondrial DNA point mutations. NGS protocols enabling the simultaneous analysis of mitochondrial and nuclear DNA are now efficient and cost-saving approaches, and have become the gold-standard technique in diagnostic laboratories.
目前，线粒体 DNA 突变的基因检测包括单核苷酸变异、几个碱基对的插入或缺失、大片段缺失或总线粒体 DNA 含量的相对耗竭的筛查。在过去十年中，下一代测序（NGS）在 线粒体疾病（MD）领域取得了显著进展，已成为诊断工作的常规步骤。
我们旨在介绍当前用于线粒体 DNA 疾病分子诊断的技术概述。我们报告了 NGS 测试对 MD 的诊断和理解的最新贡献。
NGS 技术的进步使得能够同时检测突变和异质性水平的定量，确保了检测线粒体 DNA 点突变所需的灵敏度和特异性。能够同时分析线粒体和核 DNA 的 NGS 方案现在是高效和节省成本的方法，并且已成为诊断实验室的金标准技术。
