Open Access Research

Frequency and spectrum of mitochondrial 12S rRNA variants in 440 Han Chinese hearing impaired pediatric subjects from two otology clinics

Zhisen Shen1, Jing Zheng2, Bobei Chen3, Guanghua Peng34, Ting Zhang2, Shasha Gong2, Yi Zhu25, Chuqin Zhang3, Ronghua Li6, Li Yang6, Jianjin Zhou1, Ting Cai1, Lihua Jin1, Jianxin Lu2 and Min-Xin Guan267*

Author Affiliations

1 Department of Otolaryngology, Ningbo Medical Center, Li Huili Hospital, Ningbo, Zhejiang, China

2 Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang, China

3 Department of Otolaryngology, the Second Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China

4 Department of Otolaryngology, Yuyao People's Hospital, Yuyao, Zhejiang, China

5 Department of Otolaryngology, the First Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China

6 Department of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA

7 Deparment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

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Journal of Translational Medicine 2011, 9:4  doi:10.1186/1479-5876-9-4

Published: 4 January 2011

Abstract

Background

Aminoglycoside ototoxicity is one of the common health problems. Mitochondrial 12S rRNA mutations are one of the important causes of aminoglycoside ototoxicity. However, the incidences of 12S rRNA mutations associated with aminoglycoside ototoxicity are less known.

Methods

A total of 440 Chinese pediatric hearing-impaired subjects were recruited from two otology clinics in the Ningbo and Wenzhou cities of Zhejiang Province, China. These subjects underwent clinical, genetic evaluation and molecular analysis of mitochondrial 12S rRNA. Resultant mtDNA variants were evaluated by structural and phylogenetic analysis.

Results

The study samples consisted of 227 males and 213 females. The age of all participants ranged from 1 years old to 18 years, with the median age of 9 years. Ninety-eight subjects (58 males and 40 females) had a history of exposure to aminoglycosides, accounting for 22.3% cases of hearing loss in this cohort. Molecular analysis of 12S rRNA gene identified 41 (39 known and 2 novel) variants. The incidences of the known deafness-associated 1555A > G, 1494C > T and 1095T > C mutations were 7.5%, 0.45% and 0.91% in this entire hearing-impaired subjects, respectively, and 21.4%, 2% and 2% among 98 subjects with aminoglycoside ototoxicity, respectively. The structural and phylogenetic evaluations showed that a novel 747A > G variant and known 839A > G, 1027A > G, 1310C > T and 1413T > C variants conferred increased sensitivity to aminoglycosides or nonsyndromic deafness as they were absent in 449 Chinese controls and localized at highly conserved nucleotides of this rRNA. However, other variants were polymorphisms. Of 44 subjects carrying one of definite or putative deafness-related 12S rRNA variants, only one subject carrying the 1413T > C variant harbored the 235DelC/299DelAT mutations in the GJB2 gene, while none of mutations in GJB2 gene was detected in other 43 subjects.

Conclusions

Mutations in mitochondrial 12S rRNA accounted for ~30% cases of aminoglycoside-induced deafness in this cohort. Our data strongly support the idea that the mitochondrial 12S rRNA is the hot spot for mutations associated with aminoglycoside ototoxicity. These data have been providing valuable information and technology to predict which individuals are at risk for ototoxicity, to improve the safety of aminoglycoside antibiotic therapy, and eventually to decrease the incidence of deafness.