Desquiret-Dumas Valérie, D'Ottavi Morgana, Monnin Audrey, Goudenège David, Méda Nicolas, Vizeneux Amélie, Kankasa Chipepo, Tylleskar Thorkild, Bris Céline, Procaccio Vincent, Nagot Nicolas, Van de Perre Philippe, Reynier Pascal, Molès Jean-Pierre
Department of Biochemistry and Genetics, University Hospital of Angers, F-49000 Angers, France.
UMR MITOVASC, CNRS 6015, INSERM U1083, University of Angers, F-49000 Angers, France.
Biomedicines. 2022 Jul 25;10(8):1786. doi: 10.3390/biomedicines10081786.
HIV-exposed uninfected (HEU) children show impaired health outcomes during childhood. A high rate of mitochondrial DNA (mtDNA) instability was reported in the blood of HEU at birth. We aimed to explore the relationship between these health outcomes and mtDNA deletions over time in a case series of 24 HEU children. MtDNA instability was assessed by deep sequencing and analyzed by eKLIPse-v2 algorithm at three time points, namely birth, 1 year, and 6 years of age. Association between mtDNA deletion and health outcomes, including growth, clinical, and neurodevelopmental parameters, were explored using univariate statistical analyses and after stratification with relevant variables. HEU children were selected with an equal male:female ratio. An elevated number of mtDNA deletions and duplications events was observed at 7 days' post-partum. Median heteroplasmy increased at one year of life and then returned to baseline by six years of age. The mtDNA instability was acquired and was not transmitted by the mother. No risk factors were significantly associated with mtDNA instability. In this small case series, we did not detect any association between any health outcome at 6 years and mtDNA instability measures. A significant effect modification of the association between the duration of maternal prophylaxis and child growth was observed after stratification with heteroplasmy rate. Genomic instability persists over time among HEU children but, despite its extension, stays subclinical at six years.
暴露于HIV但未感染（HEU）的儿童在童年时期健康状况受损。据报道，HEU儿童出生时血液中线粒体DNA（mtDNA）不稳定性发生率很高。我们旨在探讨在一个包含24名HEU儿童的病例系列中，这些健康状况与mtDNA缺失随时间的关系。通过深度测序评估mtDNA不稳定性，并在出生、1岁和6岁这三个时间点采用eKLIPse-v2算法进行分析。使用单变量统计分析以及在按相关变量分层后，探讨mtDNA缺失与健康状况之间的关联，包括生长、临床和神经发育参数。按男女比例相等的原则选择HEU儿童。在产后7天时观察到mtDNA缺失和重复事件的数量增加。中位异质性在1岁时增加，然后在6岁时恢复到基线水平。mtDNA不稳定性是后天获得的，并非由母亲遗传。没有危险因素与mtDNA不稳定性显著相关。在这个小病例系列中，我们未检测到6岁时的任何健康状况与mtDNA不稳定性指标之间存在任何关联。在按异质性率分层后，观察到母亲预防持续时间与儿童生长之间关联的显著效应修正。基因组不稳定性在HEU儿童中随时间持续存在，但尽管其持续存在，在6岁时仍处于亚临床状态。
