Mitochondrial DNA mutations in rRNA and tRNA loci associated with maternally inherited deafness

Objectives: Mutations in mitochondrial deoxyribonucleic acid (mtDNA) are a known cause of maternally inherited deafness and other mitochondrial disorders. These mutations often disrupt mitochondrial translation and oxidative phosphorylation, particularly affecting high-energy tissues such as the auditory system. This study aimed to identify mtDNA mutations in the 12S ribosomal RNA (rRNA), 16S rRNA, and mitochondrial transfer RNA for valine gene ( MT-TV ) loci and assess their pathogenicity using updated bioinformatic tools. Methods: A cross-sectional genetic study was performed from 2015 to 2016 involving 71 students (31 females and 40 males) aged 12–16 years, all exhibiting bilateral sensorineural hearing loss with maternal inheritance. DNA was isolated from saliva samples utilizing the phenol–chloroform technique. A 795 base pair fragment encompassing the 3’ terminus of 12S rRNA, the entire MT-TV, and the 5’ terminus of 16S rRNA was amplified and sequenced. Variants were aligned with the revised Cambridge reference sequence and evaluated utilizing the Mitochondrial transfer RNA informatics predictor (MitoTIP) pathogenicity scoring system. Results: Fifty samples produced high-quality sequences, uncovering 78 mtDNA variants. Significant mutations comprised m.1438A>G and m.1544A>T in 12S rRNA, along with m.1603A>C, m.1607T>G, and m.1623G>C in MT-TV , many of which exhibited MitoTIP scores surpassing 60%. Conclusion: Recurrent variants found in rRNA and transfer RNA loci may signify mutational hotspots responsible for maternally inherited deafness. These findings advocate for regional mtDNA screening and functional validation to enhance the diagnosis and management of mitochondrial hearing loss.