Institute of Human Genetics, Technische Universität München, München 48559, Germany
Institute of Human Genetics, Helmholtz Zentrum München, München 85764, Germany.
Essays Biochem. 2018 Jul 20;62(3):399-408. doi: 10.1042/EBC20170110.
Mitochondrial diseases present a diagnostic challenge due to their clinical and genetic heterogeneity. Achieving comprehensive molecular diagnosis via a conventional candidate-gene approach is likely, therefore, to be labour- and cost-intensive given the expanding number of mitochondrial disease genes. The advent of whole exome sequencing (WES) and whole genome sequencing (WGS) hold the potential of higher diagnostic yields due to the universality and unbiased nature of the methods. However, these approaches are subject to the escalating challenge of variant interpretation. Thus, integration of functional 'multi-omics' data, such as transcriptomics, is emerging as a powerful complementary tool in the diagnosis of mitochondrial disease patients for whom extensive prior analysis of DNA sequencing has failed to return a genetic diagnosis.
线粒体疾病由于其临床表现和遗传异质性，给诊断带来了挑战。通过传统的候选基因方法实现全面的分子诊断，由于线粒体疾病基因数量不断增加，因此可能既耗时又昂贵。全外显子组测序 (WES) 和全基因组测序 (WGS) 的出现，由于方法的普遍性和无偏性，具有更高的诊断收益潜力。然而，这些方法受到变异解释不断升级的挑战。因此，整合功能“多组学”数据，如转录组学，作为一种强大的补充工具，正在线粒体疾病患者的诊断中崭露头角，对于这些患者，广泛的 DNA 测序分析未能提供遗传诊断。
