Chakraborty Munmun, Rao Aparna, Mohanty Kuldeep
Research, L V Prasad Eye Institute, Bhubaneswar, IND.
Research, Kalinga Institute of Industrial Technology School of Biotechnology, Bhubaneswar, IND.
Cureus. 2022 Jul 21;14(7):e27129. doi: 10.7759/cureus.27129. eCollection 2022 Jul.
Background Mitochondria are essential cellular organelles that are responsible for oxidative stress-induced damage in age-dependent neurodegenerations such as glaucoma. Previous studies have linked mitochondrial DNA (mtDNA) mutations to cellular energy shortages that result in eye degeneration. Methodology To look for nucleotide variations in mtDNA in exfoliation syndrome/glaucoma (XFS/XFG), we performed a polymerase chain reaction (PCR) to amplify the entire coding region of the mitochondrial genome from peripheral blood of XFS/XFG (n = 25) patients and controls (n = 25). Results This study identified a total of 65 variations in XFS/XFG patients, of which 25 (38%) variations were non-synonymous single-nucleotide polymorphism (nsSNPs). Out of 25 nsSNPs, seven (five nsSNP in and two in gene) were predicted as pathogenic using four different software, namely, SIFT, Polyphene2, mutation taster, and MutPred2. The pathogenic nsSNPs were then subjected to structural change analysis using online tools. Conclusions The pathogenic nsSNPs were found in both proteins' transmembrane domains and were expected to be conserved, but with lower protein stability (ΔΔG <- 0.5), indicating a possibly harmful effect in exfoliation. However, three-dimensional protein analysis indicated that the predicted mutations in and were unlikely to alter the protein function.
线粒体是重要的细胞器，在年龄相关性神经退行性疾病如青光眼中，线粒体负责氧化应激诱导的损伤。先前的研究已将线粒体DNA（mtDNA）突变与导致眼部退变的细胞能量短缺联系起来。方法：为了寻找剥脱综合征/青光眼（XFS/XFG）患者线粒体DNA中的核苷酸变异，我们进行了聚合酶链反应（PCR），以扩增XFS/XFG患者（n = 25）和对照（n = 25）外周血中线粒体基因组的整个编码区。结果：本研究共鉴定出XFS/XFG患者中的65个变异，其中25个（38%）变异为非同义单核苷酸多态性（nsSNPs）。在25个nsSNPs中，使用四种不同软件（即SIFT、Polyphene2、突变预测器和MutPred2）预测有7个（基因中有5个nsSNP，基因中有2个）为致病性变异。然后使用在线工具对致病性nsSNPs进行结构变化分析。结论：在两种蛋白质的跨膜结构域中均发现了致病性nsSNPs，预计它们具有保守性，但蛋白质稳定性较低（ΔΔG < -0.5），表明在剥脱过程中可能产生有害影响。然而，三维蛋白质分析表明，基因和基因中预测的突变不太可能改变蛋白质功能。
