Thompson Whitney S, Saba Leslie, Hasadsri Linda, Girard Sylvie, Schimmenti Lisa A, Bendel-Stenzel Ellen M, Wick Myra J, Brumbaugh Jane E
Department of Clinical Genomics, Division of Neonatal Medicine, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota.
Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota.
Am J Perinatol. 2025 Jan;42(1):126-129. doi: 10.1055/s-0044-1788335. Epub 2024 Jul 15.
This study aimed to determine the prevalence and heteroplasmy level(s) of variants m.1555A > G and m.1494C > T, which are associated with aminoglycoside-induced hearing loss, in a general perinatal population. This study also aimed to characterize the association of these variants and their heteroplasmy levels with hearing loss outcomes with and without aminoglycoside exposure.
Droplet digital polymerase chain reaction was performed on 479 maternal DNA samples from a general perinatal biobank at our institution to detect the presence and heteroplasmy levels of variants m.1555A > G and m.1494C > T. Testing of paired neonatal specimen(s) was planned for positive maternal tests. A retrospective chart review was performed to characterize the population, identify aminoglycoside exposures, and determine hearing outcomes.
All maternal samples tested negative for variants m.1555A > G and m.1494C > T. Maternal and neonatal subjects had high rates of aminoglycoside exposure (15.9 and 13.9%, respectively). No subjects with sensorineural or mixed hearing loss had documented aminoglycoside exposure.
This study demonstrated that a larger sample size is needed to establish the prevalence of these variants as no subjects tested positive. Determination of variant prevalence in the neonatal population, association of variant heteroplasmy levels with hearing outcomes, and reliability of maternal testing as a surrogate for neonatal testing are important next steps toward universal prenatal or newborn screening.
· MT-RNR1 variants are associated with aminoglycoside-induced hearing loss.. · Prevalence of MT-RNR1 variants is uncertain.. · Universal screening for MT-RNR1 variants may be indicated..
本研究旨在确定一般围产期人群中与氨基糖苷类药物所致听力损失相关的m.1555A＞G和m.1494C＞T变异的患病率及异质性水平。本研究还旨在明确这些变异及其异质性水平与有无氨基糖苷类药物暴露情况下听力损失结局之间的关联。
对来自我们机构一般围产期生物样本库的479份母亲DNA样本进行液滴数字聚合酶链反应，以检测m.1555A＞G和m.1494C＞T变异的存在情况及异质性水平。若母亲检测结果为阳性，则计划对配对的新生儿样本进行检测。进行回顾性病历审查以描述人群特征、确定氨基糖苷类药物暴露情况并确定听力结局。
所有母亲样本的m.1555A＞G和m.1494C＞T变异检测均为阴性。母亲和新生儿受试者的氨基糖苷类药物暴露率较高（分别为15.9%和13.9%）。没有感音神经性或混合性听力损失的受试者有氨基糖苷类药物暴露的记录。
本研究表明，由于没有受试者检测呈阳性，因此需要更大的样本量来确定这些变异的患病率。确定新生儿人群中变异的患病率以及变异异质性水平与听力结局的关联，以及母亲检测作为新生儿检测替代方法的可靠性，是普遍产前或新生儿筛查的重要下一步。
·MT-RNR1变异与氨基糖苷类药物所致听力损失相关。·MT-RNR1变异的患病率尚不确定。·可能需要对MT-RNR1变异进行普遍筛查。
