Mutations in
mitochondrial DNA (
mtDNA) are associated with
sensorineural hearing loss. In this study, we traced the origin of the
12S rRNA C1494T mutation through analysis of the clinical, genetic, and molecular characteristics of 13 Han Chinese pedigrees with
aminoglycoside-induced and non-syndromic
bilateral hearing loss that were selected by C1494T screening in 3133 subjects with non-syndromic
hearing impairment from 27 regions of China (13/3133). Clinical evaluation revealed the variable phenotypes of
hearing impairment including severity, age-of-onset, and audiometric configuration in these subjects. Through the whole mitochondrial genome DNA sequence analysis, we identified two evolutionarily conservative variants in
protein-coding genes:
tRNA(Ala) T 5628C and
tRNA(Tyr) A5836G mutations. However, the pedigrees with these mutations did not have a higher or lower penetrance of
deafness than in other pedigrees. These results suggested that both T 5628C and A5836G mutations might not significantly modify the manifestation of the C1494T mutation. Sequencing analysis of the whole mitochondrial genome of the probands showed that 13 pedigrees from seven different provinces were classified into 10 haplogroups by the distinct sets of
mtDNA polymorphisms, including haplogroups A, B, D, D4, D4b2, F1, M, M7c, N9a1, and H2b. This result suggested that the C1494T mutation occurred sporadically with multi-origins through the evolution of the
mtDNA in China, and these
mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the C1494T mutation in these Chinese families with different penetrance of
hearing loss. In addition, the lack of a significant mutation in the GJB2 gene ruled out the possible involvement of GJB2 in the phenotypic expression of the C1494T mutation in those affected subjects. Therefore, the
aminoglycosides is solo well-established factor to contribute to the
deafness manifestation of the C1494T mutation, and prevention by avoiding the administration of
aminoglycosides in individuals carrying C1494T mutation is the most effective way to protect their vulnerability to
deafness.