Blok R B, Thorburn D R, Thompson G N, Dahl H H
Murdoch Institute, Royal Children's Hospital, Melbourne, Australia.
Hum Genet. 1995 Jan;95(1):75-81. doi: 10.1007/BF00225079.
Mitochondrial myopathies and encephalopathies can be caused by nucleotide substitutions, deletions or duplications of the mitochondrial DNA (mtDNA). In one such disorder, Kearns-Sayre Syndrome (KSS), large-scale heteroplasmic mtDNA deletions are often found. We describe a 14-year-old boy with clinical features of KSS, plus some additional features. Analysis of the entire mitochondrial genome by the polymerase chain reaction and Southern blotting revealed a 7864-bp mtDNA deletion, heteroplasmic in its tissue distribution. DNA sequencing established that the deletion was between nucleotides 6238 and 14,103, and flanked by a 4-bp (TCCT) direct repeat sequence. Deletions between direct repeats have been hypothesised to occur by a slipped-mismatching or illegitimate recombination event, or following the DNA cleavage action of topoisomerase II. Analysis of the gene sequence in the region surrounding the mtDNA deletion breakpoint in this patient revealed the presence of putative vertebrate topoisomerase II sites. We suggest that direct repeat sequences, together with putative topoisomerase II sites, may predispose certain regions of the mitochondrial genome to deletions.
线粒体肌病和脑病可由线粒体DNA（mtDNA）的核苷酸替换、缺失或重复引起。在一种这样的疾病——卡恩斯-塞尔综合征（KSS）中，经常发现大规模的异质性mtDNA缺失。我们描述了一名14岁男孩，具有KSS的临床特征以及一些其他特征。通过聚合酶链反应和Southern印迹法对整个线粒体基因组进行分析，发现了一个7864碱基对的mtDNA缺失，其在组织分布上是异质性的。DNA测序确定该缺失位于核苷酸6238和14103之间，并由一个4碱基对（TCCT）的直接重复序列侧翼。据推测，直接重复序列之间的缺失是由滑动错配或非法重组事件引起的，或者是在拓扑异构酶II的DNA切割作用之后发生的。对该患者mtDNA缺失断点周围区域的基因序列分析显示存在推定的脊椎动物拓扑异构酶II位点。我们认为，直接重复序列与推定的拓扑异构酶II位点一起，可能使线粒体基因组的某些区域易于发生缺失。
