Abstract
Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. We report here a systematic mutational screening of the mitochondrial 12S rRNA gene in 128 Chinese pediatric subjects with sporadic aminoglycoside-induced and non-syndromic hearing loss. We show that aminoglycoside ototoxicity accounts for 48% of cases of hearing loss in this Chinese pediatric population. Of the known deafness-associated mutations in this gene, the incidence of the A1555G mutation is ~13% and ~2.9% in this Chinese pediatric population with aminoglycoside-induced and non-syndromic hearing loss, respectively. Furthermore, mutations at position 961 in the 12S rRNA gene account for ~1.7% and 4.4% of cases of aminoglycoside-induced and non-syndromic hearing loss in this Chinese clinical population, respectively. The T1095C mutation has been identified in one maternally inherited family with aminoglycoside-induced and non-syndromic hearing loss. However, the C1494T mutation was not detected in this clinical population. In addition, three variants, A827G, T1005C and A1116G, in the 12S rRNA gene, localized at highly conserved sites, may play a role in the pathogenesis of aminoglycoside ototoxicity. These data strongly suggest that the mitochondrial 12S rRNA is a hot-spot for deafness-associated mutations in the Chinese population.
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Acknowledgements
This work was supported by National Institutes of Health (NIH) grants DC05230, DC04958 from the National Institute on Deafness and Other Communication Disorders, and a grant award 2004CCA02200 from National Basic Research Priorities Programme of China to M.X.G.. We thank the family members for their participation and support in this study.
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Z. Li and R. Li contributed equally to this work.
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Li, Z., Li, R., Chen, J. et al. Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss. Hum Genet 117, 9–15 (2005). https://doi.org/10.1007/s00439-005-1276-1
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DOI: https://doi.org/10.1007/s00439-005-1276-1