Institut für Humangenetik, Klinikum rechts der Isar, Technische Universität München, Trogerstraße 32, 81675 München, Germany; Institute of Neurogenomics, Helmholtz Zentrum München, Ingolstaedter Landstraße 1, D-85764 Neuherberg, Germany.
Institut für Humangenetik, Klinikum rechts der Isar, Technische Universität München, Trogerstraße 32, 81675 München, Germany; Institute of Neurogenomics, Helmholtz Zentrum München, Ingolstaedter Landstraße 1, D-85764 Neuherberg, Germany.
EBioMedicine. 2020 Jun;56:102784. doi: 10.1016/j.ebiom.2020.102784. Epub 2020 May 23.
Mitochondrial diseases are amongst the most genetically and phenotypically diverse groups of inherited diseases. The vast phenotypic overlap with other disease entities together with the absence of reliable biomarkers act as driving forces for the integration of unbiased methodologies early in the diagnostic algorithm, such as whole exome sequencing (WES) and whole genome sequencing (WGS). Such approaches are used in variant discovery and in combination with high-throughput functional assays such as transcriptomics in simultaneous variant discovery and validation. By capturing all genes, they not only increase the diagnostic rate in heterogenous mitochondrial disease patients, but accelerate novel disease gene discovery, and are valuable in side-stepping the risk of overlooking unexpected or even treatable genetic disease diagnoses.
线粒体疾病是遗传疾病中基因和表型最为多样化的疾病之一。与其他疾病实体的巨大表型重叠，以及缺乏可靠的生物标志物，成为在诊断算法早期整合无偏方法的驱动力，如外显子组测序 (WES) 和全基因组测序 (WGS)。这些方法用于变异发现，并与高通量功能测定（如转录组学）相结合，用于同时进行变异发现和验证。通过捕获所有基因，它们不仅提高了异质性线粒体疾病患者的诊断率，而且加速了新的疾病基因的发现，并且在避免忽略意外甚至可治疗的遗传疾病诊断方面具有重要价值。
