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 cellfree DNA obtained from maternal plasma can successfully detect m.1555A > G and m.1494C > T mutations.

Application of the TaqMan ARMS-PCR Approach for Genotyping Drug-Induced Hearing Loss Using Dried Blood Samples

“…Among the genetic causes of deafness, mutations in mtDNA are closely associated with aminoglycoside-induced deafness and non-syndromic deafness. Studies have shown that the 1555A>G and 1494C>T mutations in mtDNA are the genetic basis for maternally inherited aminoglycoside-induced deafness, with aminoglycoside antibiotics being the main cause of deafness [3,4]. The prevalence of mtDNA mutations varies among different regions worldwide, with the occurrence rate of the 1555A>G mutation ranging from 0.08% to 0.7% in the general population and from 0.42% to 17% in the deaf population.…”