Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Biochem Biophys Res Commun. 2010 Mar 19;393(4):740-5. doi: 10.1016/j.bbrc.2010.02.072. Epub 2010 Feb 18.
Patients with mitochondrial DNA disease are amongst the most challenging to diagnose and manage given the striking phenotypic and genetic heterogeneity, which characterise these conditions. Recently, we and others have demonstrated the m.3243A>G mutation, one of the most common mitochondrial DNA pathogenic mutations, is present at clinically relevant levels in urinary epithelium, thus providing a practical, non-invasive test for diagnosis and mutation screening. In this study we further evaluate the use of these cells in detecting the m.3243A>G mutation, other mtDNA tRNA gene point mutations including the m.8344A>G mutation and single large-scale mtDNA deletions. We observe a robust relationship between m.3243A>G levels in urothelial cells and clinically affected tissues that does not change with time. Conversely, single large-scale mtDNA deletions can be detected in urothelial cells, with higher levels present in younger patients with more severe disease, but generally mtDNA deletion levels are not representative of those seen in a clinically affected tissue. Our results have implications for the diagnosis, management and counselling of families with mtDNA disease.
患有线粒体 DNA 疾病的患者由于其明显的表型和遗传异质性，诊断和管理极具挑战性，这些情况就是其特征。最近，我们和其他人已经证明，m.3243A>G 突变，最常见的线粒体 DNA 致病性突变之一，在尿路上皮中以临床相关的水平存在，从而为诊断和突变筛查提供了一种实用的、非侵入性的检测方法。在这项研究中，我们进一步评估了这些细胞在检测 m.3243A>G 突变、其他 mtDNA tRNA 基因突变（包括 m.8344A>G 突变）和单个大片段 mtDNA 缺失方面的应用。我们观察到尿路上皮细胞中的 m.3243A>G 水平与临床受累组织之间存在着很强的相关性，这种相关性不会随时间而改变。相反，可以在尿路上皮细胞中检测到单个大片段 mtDNA 缺失，在病情更严重的年轻患者中，缺失水平更高，但一般来说，mtDNA 缺失水平并不能代表临床受累组织中的水平。我们的研究结果对线粒体 DNA 疾病患者的诊断、管理和咨询具有重要意义。
