Mitochondrial genetic diseases can result from defects in mitochondrial DNA (mtDNA) in the form of deletions, point mutations, or depletion, which ultimately cause loss of oxidative phosphorylation. These mutations may be spontaneous, maternally inherited, or a result of inherited nuclear defects in genes that maintain mtDNA. This review focuses on our current understanding of nuclear gene mutations that produce mtDNA alterations and cause mitochondrial depletion syndrome (MDS), progressive external ophthalmoplegia (PEO), ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). To date, all of these etiologic nuclear genes fall into one of two categories: genes whose products function directly at the mtDNA replication fork, such as POLG, POLG2, and TWINKLE, or genes whose products supply the mitochondria with deoxynucleotide triphosphate pools needed for DNA replication, such as TK2, DGUOK, TP, SUCLA2, ANT1, and possibly the newly identified MPV17.

中文翻译：

---

DNA复制的线粒体疾病。

线粒体遗传病可能是由线粒体DNA（mtDNA）的缺陷，缺失，点突变或耗竭等导致的，最终导致氧化磷酸化的丧失。这些突变可能是自发的，母体遗传的，或者是维持mtDNA的基因中遗传性核缺陷的结果。这项审查侧重于我们目前对产生mtDNA改变并引起线粒体耗竭综合征（MDS），进行性眼外肌麻痹（PEO），共济失调性神经病或线粒体神经胃肠道脑病（MNGIE）的核基因突变的了解。迄今为止，所有这些病因性核基因都属于以下两类之一：其产物直接在mtDNA复制叉上起作用的基因，例如POLG，POLG2和TWINKLE，