Zeviani M, Servidei S, Gellera C, Bertini E, DiMauro S, DiDonato S
Istituto Neurologico C. Besta, Laboratory of Biochemistry and Genetics, Milano, Italy.
Nature. 1989 May 25;339(6222):309-11. doi: 10.1038/339309a0.
Deletions of muscle mitochondrial DNA (mtDNA) have recently been found in patients with mitochondrial myopathy. However, as most of the described cases were sporadic, and individual deletions involved different portions of mtDNA, the mechanism(s) producing the molecular lesions, as well as their mode of transmission, remain unclear. By studying families with mtDNA heteroplasmy, valuable information can be obtained about the role of inheritable factors in the pathogenesis of these disorders. We have studied four members of a family with autosomal dominant mitochondrial myopathy. Multiple deletions, involving the same portion of muscle mtDNA, were identified in all patients. Sequence analysis of the mutant mtDNAs, performed after DNA amplification by the polymerase-chain reaction showed that all the deletions start within a 12-nucleotide stretch at the 5' end of the D-loop region, a site of active communication between the nucleus and the mtDNA. The data indicate that a mutation of a nuclear-coded protein can destroy the integrity of the mitochondrial genome in a specific, heritable way.
近期，在线粒体肌病患者中发现了肌肉线粒体DNA（mtDNA）缺失。然而，由于大多数已报道的病例为散发性，且个体缺失涉及mtDNA的不同部分，产生分子损伤的机制及其传播方式仍不清楚。通过研究存在mtDNA异质性的家族，可获得关于遗传因素在这些疾病发病机制中作用的有价值信息。我们研究了一个患常染色体显性线粒体肌病家族的四名成员。在所有患者中均鉴定出涉及肌肉mtDNA相同部分的多个缺失。通过聚合酶链反应进行DNA扩增后，对突变mtDNA进行的序列分析表明，所有缺失均始于D环区域5'端的一个12个核苷酸的片段内，该区域是细胞核与mtDNA之间活跃通讯的位点。数据表明，核编码蛋白的突变可通过特定的、可遗传的方式破坏线粒体基因组的完整性。
