Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Convergence Medicine and Stem Cell Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Pediatr Res. 2021 Nov;90(5):1016-1022. doi: 10.1038/s41390-020-01358-6. Epub 2021 Jan 27.
There has been a growing interest in the association between mitochondrial dysfunction and sepsis. However, most studies have focused on mitochondrial structural damage, functional aspects, or the clinical phenotypes in sepsis. The purpose of this study was to evaluate mitochondrial DNA (mtDNA) gene mutations in critically ill pediatric patients with septic shock.
Thirteen patients with severe sepsis or septic shock admitted to the pediatric intensive care unit (PICU) of a tertiary children's hospital were enrolled in this prospective observational study. Clinical data from electronic medical records were obtained. Whole-blood samples were collected within 24 h of PICU admission to perform PBMC isolation, mtDNA extraction, and mtDNA sequencing using next-generation sequencing.
mtDNA sequencing revealed mutations in 9 of the 13 patients, presenting 27 point mutations overall, with 15 (55.6%) located in the locus related to adenosine triphosphate production and superoxide metabolism, including electron transport.
In this pilot study, significant numbers of mtDNA point mutations were detected in critically ill pediatric patients with septic shock. These mutations could provide promising evidence for mitochondrial dysfunction in sepsis and a basis for further large-scale studies.
This study is the first to examine mitochondrial DNA mutations in pediatric patients with septic shock using next-generation sequencing. A high frequency of mitochondrial DNA mutations was detected in these patients indicating an association with septic shock. This pilot study may provide a potential explanation for the association between mitochondrial dysfunction and septic shock on a genetic basis.
线粒体功能障碍与脓毒症之间的关联引起了越来越多的关注。然而，大多数研究都集中在脓毒症中的线粒体结构损伤、功能方面或临床表型上。本研究旨在评估患有感染性休克的危重症儿科患者中线粒体 DNA（mtDNA）基因突变情况。
本前瞻性观察研究纳入了 13 名入住三级儿童医院儿科重症监护病房（PICU）的严重脓毒症或感染性休克患者。从电子病历中获取临床数据。在入住 PICU 的 24 小时内采集全血样本，以进行 PBMC 分离、mtDNA 提取和使用下一代测序进行 mtDNA 测序。
mtDNA 测序显示 13 名患者中有 9 名存在突变，总共出现 27 个点突变，其中 15 个（55.6%）位于与三磷酸腺苷生成和超氧化物代谢相关的位置，包括电子传递。
在这项初步研究中，检测到严重脓毒症感染性休克的危重症儿科患者中存在大量 mtDNA 点突变。这些突变可能为脓毒症中线粒体功能障碍提供了有希望的证据，并为进一步的大规模研究奠定了基础。
本研究首次使用下一代测序技术检查感染性休克的儿科患者的线粒体 DNA 突变。这些患者中检测到大量线粒体 DNA 突变，表明其与感染性休克有关。这项初步研究可能从遗传基础上为线粒体功能障碍与感染性休克之间的关联提供了潜在解释。
