CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad 500007, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Genes (Basel). 2021 Aug 24;12(9):1300. doi: 10.3390/genes12091300.
Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder that causes loss of central vision. Three primary variants (m.3460G>A, m.11778G>A, and m.14484T>C) and about 16 secondary variants are responsible for LHON in the majority of the cases. We investigated the complete mitochondrial DNA (mtDNA) sequences of 189 LHON patients and found a total of 54 disease-linked pathogenic variants. The primary variants m.11778G>A and m.14484T>C were accountable for only 14.81% and 2.64% cases, respectively. Patients with these two variants also possessed additional disease-associated variants. Among 156 patients who lacked the three primary variants, 16.02% harboured other LHON-associated variants either alone or in combination with other disease-associated variants. Furthermore, we observed that none of the haplogroups were explicitly associated with LHON. We performed a meta-analysis of m.4216T>C and m.13708G>A and found a significant association of these two variants with the LHON phenotype. Based on this study, we recommend the use of complete mtDNA sequencing to diagnose LHON, as we found disease-associated variants throughout the mitochondrial genome.
Leber 遗传性视神经病变（LHON）是一种线粒体疾病，可导致中心视力丧失。三种主要变体（m.3460G>A、m.11778G>A 和 m.14484T>C）和大约 16 种次要变体在大多数情况下导致 LHON。我们研究了 189 名 LHON 患者的完整线粒体 DNA（mtDNA）序列，共发现了 54 种与疾病相关的致病性变体。主要变体 m.11778G>A 和 m.14484T>C 分别仅占 14.81%和 2.64%的病例。携带这些两种变体的患者还存在其他与疾病相关的变体。在缺乏三种主要变体的 156 名患者中，16.02%单独或与其他与疾病相关的变体一起携带其他 LHON 相关变体。此外，我们观察到没有任何单倍群与 LHON 明确相关。我们对 m.4216T>C 和 m.13708G>A 进行了荟萃分析，发现这两种变体与 LHON 表型显著相关。基于这项研究，我们建议使用完整的 mtDNA 测序来诊断 LHON，因为我们在整个线粒体基因组中发现了与疾病相关的变体。
