Maternally transmitted aminoglycoside-induced and non-syndromic hearing loss caused by the 1494C > T mutation in the mitochondrial 12S rRNA gene in two Chinese families

Abstract

Objective: To explore the molecular genetic characterization of two Chinese families with aminoglycoside-induced and non-syndromic hearing loss (NSHL). Design:Clinical evaluations, sequence analysis of mitochondrial DNA (mtDNA) as well as two nuclear genes TRMU and MTO1 encoding mitochondrial proteins. Study sample: Two Chinese families with aminoglycoside-induced and NSHL. Results: Clinical evaluations revealed incomplete penetrance (28.6% vs. 40.0%) and variable phenotype of hearing losses between two families. When the effect of aminoglycosides was excluded, the penetrances were both 0%. Sequence analysis of mitochondrial genomes showed a homoplasmic 1494C > T mutation in the12S rRNA gene (MT-RNR1) in all maternal relatives, as well as distinct sets of mtDNA polymorphism belonging to Eastern Asian haplogroups D4j and D5a2, respectively. However, none of these mtDNA variants was highly evolutionarily conserved and implicated to have functional significance. No mutations were identified in either TRMU or MTO1 gene. Conclusions: Mitochondrial 1494C> T mutation is the molecular basis responsible for the NSHL of two families, and the use of aminoglycoside antibiotics can worsen the hearing of the mutation carriers. Our results indicate the importance of a systematic screening for the mitochondrial 1494C > T mutation in Chinese subjects in the prevention of aminoglycoside-induced and non-syndromic hearing loss.

Key Words::

• Hearing loss
• mitochondrial DNA
• 12S rRNA/MT-RNR1
• aminoglycoside ototoxicity
• nuclear background
• haplogroups

Acknowledgements

This study was supported by the research grant award from Jiangsu Health Administration (LJ201120), and the research grant award from the National Natural Science Foundation of China (No. 31171217), and a grant funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

Declaration of interest: The authors report no declarations of interest.