The detection of MT-RNR1 gene m.1555A>G mutation among the cases with non-syndromic deafness

Abstract

Background: More than 200 genetic mutations of deafness have been identified. Among them, m.1555A>G and m.1494C>T mutations of the MT-RNR1 gene encoding the 12S rRNA of the mitochondrial genome are unique in causing drug-induced non-syndromic deafness.1 Specifically, carriers of the m.1555G or m.1494T mutant allele have normal hearing, but acquired hearing loss after taking aminoglycoside antibiotics. In other words, if the carrier of the above mutant allele does not use aminoglycoside antibiotics, it is possible to prevent hearing loss. International clinical practice recommends mandatory testing of m.1555A>G and m.1494C>T mutations in newborns or clients before starting aminoglycoside antibiotics. This type of analysis has not yet entered clinical practice in Mongolia. Also, the lack of research data on the distribution of the above mutations and the genetic causes of non-medication-induced deafness is the reason for conducting this study. Aim: The purpose of this study was to detect m.1555A>G, m.1494C>T mutations of the MT-RNR1 gene encoding mitochondrial 12S rRNA in cases with non-syndromic deafness by real-time polymerase chain reaction (qPCR) method, and to determine the genealogy of each mutated case and its family. Materials and Methods: 261 people with non-syndromic deafness and hearing loss who volunteered to participate in the study. Audiometric tests were performed on study participants, and molecular biology tests were performed on 17 people with a history of drug-induced hearing loss. The blood sample was taken from the participants, DNA was extracted and purified, and the results were obtained by qPCR to detect m.1555A>G and m.1494C>T mutations. The sequencing was performed to confirm all cases in which mutant alleles were detected. Results: Of the total participants, 58% were male (n=152) and 42% were female (n=110). When hearing loss was classified by clinical diagnosis based on audiometry, 46.7% (n=122) had deafness, 24.1% (n=63) had sensorineural deafness, 11.1% (n=29) had sensorineural hearing loss, and 2.29% (n=29) had sensorineural hearing loss. =6) had conductive hearing loss, and 15.7% (n=41) had cochlear implants. In 17 cases of drug-induced hearing loss, m.1555G mutation was detected in one case. The mutation-positive case was considered as the proband, followed by clinical-genealogical family and genealogy, samples were taken from 2 members of the proband’s family to detect the mutation, and the m.1555G mutation was also detected in PCR analysis. Conclusion: In our study, we detected the m.1555A>G mutation of the MT-RNR1 gene by qPCR among cases of drug-induced hearing loss, and we were able to detect the same mutation in 2 of his family members who agreed to participate in the study.