通过非侵入性产前检测发现与氨基糖苷类耳毒性相关的线粒体突变。

Detecting mitochondrial mutations associated with aminoglycoside ototoxicity by noninvasive prenatal testing.

机构信息

Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.

Dongguan Maternal and Child Health Hospital, Dongguan, China.

出版信息

J Clin Lab Anal. 2023 Jan;37(1):e24827. doi: 10.1002/jcla.24827. Epub 2022 Dec 29.

DOI:10.1002/jcla.24827

PMID:36579624

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9833975/

Abstract

OBJECTIVES

Numerous diseases and disorders are associated with mitochondrial DNA (mtDNA) mutations, among which m.1555A > G and m.1494C > T mutations in the 12 S ribosomal RNA gene contribute to aminoglycoside-induced and nonsyndromic hearing loss worldwide.

METHODS

A total of 76,842 qualified non-invasive prenatal (NIPT) samples were subjected to mtDNA mutation and haplogroup analysis.

RESULTS

We detected 181 m.1555A > G and m.1494C > T mutations, 151 of which were subsequently sequenced for full-length mitochondrial genome verification. The positive predictive values for the m.1555A > G and m.1494C > T mutations were 90.78% and 90.00%, respectively, a performance comparable to that attained with newborn hearing screening. Furthermore, mitochondrial haplogroup analysis revealed that the 12 S rRNA 1555A > G mutation was enriched in sub-haplotype D5[p = 0, OR = 4.6706(2.81-7.78)].

CONCLUSIONS

Our findings indicate that the non-invasive prenatal testing of cell-free DNA obtained from maternal plasma can successfully detect m.1555A > G and m.1494C > T mutations.

摘要

目的

许多疾病和障碍都与线粒体 DNA (mtDNA) 突变有关，其中 12S 核糖体 RNA 基因中的 m.1555A>G 和 m.1494C>T 突变导致全球范围内的氨基糖苷类药物诱导和非综合征性听力损失。

方法

对总共 76842 例合格的非侵入性产前 (NIPT) 样本进行 mtDNA 突变和单倍群分析。

结果

我们检测到 181 例 m.1555A>G 和 m.1494C>T 突变，其中 151 例随后进行了全长线粒体基因组验证测序。m.1555A>G 和 m.1494C>T 突变的阳性预测值分别为 90.78%和 90.00%，与新生儿听力筛查相当。此外，线粒体单倍群分析显示，12S rRNA 1555A>G 突变在亚单倍型 D5 中富集（p=0，OR=4.6706（2.81-7.78））。