Objectives: Mutations in mitochondrial tRNA (mt-tRNA) are the important causes for maternally inherited hypertension, however, the pathophysiology of mt-tRNA mutations in clinical expression of hypertension remains poorly understood. Material and Methods: In this study, we report the molecular features of a Han Chinese pedigree with maternally transmitted essential hypertension. The entire mitochondrial genomes are PCR amplified and sequenced, Moreover, phylogenetic analysis, haplogroup analysis, as well as pathogenicity scoring system are used to assess the potential roles for mtDNA mutations. Results: Strikingly, among ten matrilineal relatives, three of them suffer from variable degree of hypertension at different age at onset. Sequence analysis of the complete mitochondrial genomes suggests the presence of three possible pathogenic mtDNA mutations: tRNAAsp T7561C, tRNAHis C12153T and A12172G, together with a set of variants belonging to East Asian mitochondrial haplogroup M7a. Interestingly, the T7561C mutation occurs at position 44 in the variable region of tRNAAsp, while the C12153T and A12172G mutations are localized at extremely conserved nucleotides in the D-arm and anticodon stem of tRNAHis gene, respectively, which are critical for tRNA steady-state level and function. Conclusions: Mitochondrial T7561C, C12153T and A12172G mutations may lead to the failure in tRNAs metabolism, and cause mitochondrial dysfunction that is responsible for hypertension. However, the homoplasmy form of mt-tRNA mutations, incomplete penetrance of hypertension suggest that T7561C, C12153T and A12172G mutations are insufficient to produce the clinical phenotype, hence, other risk factors such as environmental factors, nuclear genes and epigenetic modifications may contribute to the phenotypic manifestation of maternally inherited hypertension in this Chinese pedigree.


中文翻译：

---

线粒体 tRNAAsp T7561C、tRNAHis C12153T 和 A12172G 突变可能与汉族血统中的原发性高血压有关

目的：线粒体 tRNA (mt-tRNA) 突变是母系遗传性高血压的重要原因，然而，mt-tRNA 突变在高血压临床表达中的病理生理学仍知之甚少。材料和方法：在这项研究中，我们报告了一个母系传播的原发性高血压汉族血统的分子特征。整个线粒体基因组经过 PCR 扩增和测序，此外，系统发育分析、单倍群分析以及致病性评分系统用于评估 mtDNA 突变的潜在作用。结果：引人注目的是，在10名母系亲属中，有3名在不同年龄发病时患有不同程度的高血压。完整线粒体基因组的序列分析表明存在三种可能的致病性 mtDNA 突变：tRNAAsp T7561C、tRNAHis C12153T 和 A12172G，以及一组属于东亚线粒体单倍群 M7a 的变体。有趣的是，T7561C 突变发生在 tRNAAsp 可变区的第 44 位，而 C12153T 和 A12172G 突变分别位于 tRNAHis 基因的 D 臂和反密码子茎中极其保守的核苷酸，这对 tRNA 稳态至关重要水平和功能。结论：线粒体 T7561C、C12153T 和 A12172G 突变可能导致 tRNAs 代谢失败，并导致导致高血压的线粒体功能障碍。然而，mt-tRNA 突变的同质形式、高血压的不完全外显率表明 T7561C、