Mitochondrial disease genetics update: recent insights into the molecular diagnosis and expanding phenotype of primary mitochondrial disease.
Mitochondrial disease genetics update: recent insights into the molecular diagnosis and expanding phenotype of primary mitochondrial disease.
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DOI：
10.1097/mop.0000000000000686
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发表时间：
2018-12
影响因子：
3.6
通讯作者：
Falk MJ
中科院分区：
文献类型：
--
作者：
McCormick EM;Zolkipli-Cunningham Z;Falk MJ
原发性线粒体疾病（PMD）是一组遗传和表型多样的遗传性能量缺乏症，其由受损的线粒体氧化磷酸化（OXPHOS）能力引起。线粒体和核基因组中超过350个基因的突变现在被认为会导致每种遗传模式的原发性线粒体疾病。下一代测序技术大大加快了线粒体疾病基因的发现和诊断效率。在这里，我们提供了一个最新的审查，最近确定的，新的线粒体疾病基因和/或致病性变异，直接损害线粒体的结构，动力学和/或功能。对过去12个月的PubMed出版物进行了审查，确定了16个新的PMD基因和/或致病性变体，以及对各种线粒体疾病基因的扩展表型识别。广泛的外显子组测序已成为PMD的标准一线诊断方法。这促进了更快速和准确的疾病识别，并大大扩展了对广泛的不同临床表型的理解。PMD诊断的全面双基因组测序方法继续提高诊断率，推进对线粒体生理学的理解，并为开发针对线粒体疾病病理生理学各个方面的精确治疗提供强大的潜力。
Primary Mitochondrial Disease (PMD) are a genetically and phenotypically diverse group of inherited energy deficiency disorders caused by impaired mitochondrial oxidative phosphorylation (OXPHOS) capacity. Mutations in more than 350 genes in both mitochondrial and nuclear genomes are now recognized to cause primary mitochondrial disease following every inheritance pattern. Next-generation sequencing technologies have dramatically accelerated mitochondrial disease gene discovery and diagnostic yield. Here, we provide an up-to-date review of recently-identified, novel mitochondrial disease genes and/or pathogenic variants that directly impair mitochondrial structure, dynamics, and/or function. A review of PubMed publications was performed from the past 12 months that identified 16 new PMD genes and/or pathogenic variants, as well as expanded phenotype recognition for a wide variety of mitochondrial disease genes. Broad-based exome sequencing has become the standard first-line diagnostic approach for PMD. This has facilitated more rapid and accurate disease identification, and greatly expanded understanding of the wide spectrum of distinct clinical phenotypes. A comprehensive dual-genome sequencing approach to PMD diagnosis continues to improve diagnostic yield, advance understanding of mitochondrial physiology, and provide strong potential to develop precision therapeutics targeted to diverse aspects of mitochondrial disease pathophysiology.