Duan Hong, Huang Sha-Sha, Zhu Feng-Jiao, Wang Guo-Jian, Gao Xue, Yuan Yong-Yi, Dai Pu
Department of Otolaryngology, The Third People's Hospital of Shenzhen, Shenzhen, China.
Otolaryngology Head and Neck Surgery, Chinese People's Liberation Army (PLA) General Hospital, Beijing, P.R. China.
Medicine (Baltimore). 2025 Jun 27;104(26):e43066. doi: 10.1097/MD.0000000000043066.
Genetic variants, many of which are in mitochondrial DNA (mtDNA), contribute to hearing loss. Screening for these variants facilitates the identification of potential carriers, as many people with these mutations do not show hearing loss at birth but show late-onset hearing loss. We conducted a population-based cohort study involving 180,458 neonates born in Beijing, China. Hearing screening was performed through detailed counseling and systematic health assessment. The patient's peripheral blood was collected, and the variants was screened by next generation sequencing. An investigation of 142 probands and their matrilineal family members indicated a homoplasmic or heteroplasmic mtDNA mutation (adenine-to-guanine mutation at position 1555 in mtDNA 12S rRNA [A1555G] or cytosine-to-thymine mutation at position 1494 in mtDNA 12S rRNA) incidence of 0.227% (409 individuals). In total, 71.8% of the probands carried the homoplasmic A1555G mutation, 21.1% had the heteroplasmic A1555G mutation, and the remaining 7.1% had the homoplasmic cytosine-to-thymine mutation at position 1494 in mtDNA 12S rRNA mutation. A mtDNA haplotype analysis showed that 50.8% of the cases belonged to haplogroup D, the predominant haplotype in this Chinese population. Individuals with haplogroups B and M, which accounted for 10.7% and 9.0% of all cases, respectively, tended to have lower hearing thresholds at higher frequencies. We found no significant difference in the rate of hearing loss between vaccinated and unvaccinated individuals with mtDNA mutations, suggesting that the amounts of aminoglycoside antibiotics contained in vaccines were insufficient to induce hearing loss. This study reveals the incidence of mtDNA variants in the largest population studied to date and establishes that carriers of mtDNA variants can safely receive vaccines with no or low aminoglycoside antibiotic levels. This study provides a paradigm for studying the impact of these mtDNA variants on disease pathogenesis and the effects of mediation strategies.
基因变异（其中许多存在于线粒体DNA [mtDNA] 中）会导致听力损失。筛查这些变异有助于识别潜在携带者，因为许多携带这些突变的人在出生时并未表现出听力损失，而是表现为迟发性听力损失。我们在中国北京开展了一项基于人群的队列研究，涉及180458名新生儿。通过详细咨询和系统健康评估进行听力筛查。采集患者外周血，通过下一代测序筛查变异。对142名先证者及其母系家庭成员的调查显示，同质性或异质性mtDNA突变（mtDNA 12S rRNA第1555位腺嘌呤到鸟嘌呤突变 [A1555G] 或mtDNA 12S rRNA第1494位胞嘧啶到胸腺嘧啶突变）的发生率为0.227%（409人）。总体而言，71.8%的先证者携带同质性A1555G突变，21.1%携带异质性A1555G突变，其余7.1%携带mtDNA 12S rRNA第1494位胞嘧啶到胸腺嘧啶的同质性突变。mtDNA单倍型分析表明，50.8%的病例属于D单倍群，这是该中国人群中的主要单倍型。分别占所有病例10.7%和9.0%的B单倍群和M单倍群个体在较高频率下往往具有较低的听力阈值。我们发现携带mtDNA突变的接种疫苗者和未接种疫苗者之间的听力损失发生率没有显著差异，这表明疫苗中含有的氨基糖苷类抗生素量不足以导致听力损失。本研究揭示了迄今为止所研究的最大人群中mtDNA变异的发生率，并确定mtDNA变异携带者可以安全接种不含或含低水平氨基糖苷类抗生素的疫苗。本研究为研究这些mtDNA变异对疾病发病机制的影响以及调节策略的效果提供了一个范例。
