Detecting mitochondrial mutations associated with aminoglycoside ototoxicity by noninvasive prenatal testing

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.