Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.
Department of Paediatrics, University of Melbourne, Melbourne, VIC 3052, Australia.
Genes (Basel). 2021 Apr 20;12(4):607. doi: 10.3390/genes12040607.
Mitochondrial diseases can be caused by pathogenic variants in nuclear or mitochondrial DNA-encoded genes that often lead to multisystemic symptoms and can have any mode of inheritance. Using a single test, Genome Sequencing (GS) can effectively identify variants in both genomes, but it has not yet been universally used as a first-line approach to diagnosing mitochondrial diseases due to related costs and challenges in data analysis. In this article, we report three patients with mitochondrial disease molecularly diagnosed through GS performed on DNA extracted from blood to demonstrate different diagnostic advantages of this technology, including the detection of a low-level heteroplasmic pathogenic variant, an intragenic nuclear DNA deletion, and a large mtDNA deletion. Current technical improvements and cost reductions are likely to lead to an expanded routine diagnostic usage of GS and of the complementary "Omic" technologies in mitochondrial diseases.
线粒体疾病可由核或线粒体 DNA 编码基因中的致病变异体引起，常导致多系统症状，并可具有任何遗传方式。使用单一检测方法——全基因组测序（GS），可以有效地识别两个基因组中的变异体，但由于相关成本和数据分析方面的挑战，它尚未被普遍用作线粒体疾病的一线诊断方法。在本文中，我们报告了通过对血液中提取的 DNA 进行 GS 检测，分子诊断为线粒体疾病的 3 名患者，以展示该技术的不同诊断优势，包括检测低水平异质体致病性变异体、基因内核 DNA 缺失和大片段 mtDNA 缺失。当前技术的改进和成本的降低可能会导致 GS 以及互补的“组学”技术在线粒体疾病中的常规诊断应用得到扩展。
