MRC-Mitochondrial Biology Unit, MRC MBU, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, UK.
J Inherit Metab Dis. 2017 Jul;40(4):587-599. doi: 10.1007/s10545-017-0027-5. Epub 2017 Mar 21.
A large group of mitochondrial disorders, ranging from early-onset pediatric encephalopathic syndromes to late-onset myopathy with chronic progressive external ophthalmoplegia (CPEOs), are inherited as Mendelian disorders characterized by disturbed mitochondrial DNA (mtDNA) maintenance. These errors of nuclear-mitochondrial intergenomic signaling may lead to mtDNA depletion, accumulation of mtDNA multiple deletions, or both, in critical tissues. The genes involved encode proteins belonging to at least three pathways: mtDNA replication and maintenance, nucleotide supply and balance, and mitochondrial dynamics and quality control. In most cases, allelic mutations in these genes may lead to profoundly different phenotypes associated with either mtDNA depletion or multiple deletions.
一大类线粒体疾病，从早发性小儿脑病综合征到迟发性伴有慢性进行性眼外肌麻痹（CPEO）的肌病，均作为孟德尔疾病遗传，其特征是线粒体 DNA（mtDNA）维持受到干扰。这些核-线粒体基因组间信号的错误可能导致关键组织中 mtDNA 耗竭、mtDNA 大量缺失的积累，或者两者兼而有之。涉及的基因编码属于至少三种途径的蛋白质：mtDNA 复制和维持、核苷酸供应和平衡以及线粒体动力学和质量控制。在大多数情况下，这些基因的等位基因突变可能导致与 mtDNA 耗竭或大量缺失相关的截然不同的表型。
