Mutations in the
mitochondrial DNA have been associated with
hearing loss. However, the prevalence and spectrum of mitochondrial
tRNA mutations in hearing-impaired subjects are poorly understood. In this report, we have investigated the prevalence and spectrum of mitochondrial
tRNA(Ser(UCN)) mutations in a large cohort of 2651 Han Chinese subjects with
hearing loss. The clinical evaluation showed that 744 subjects (432 males and 312 females) had a history of exposure to
aminoglycosides and other probands exhibited
nonsyndromic hearing loss. Mutational analysis of
tRNA(Ser(UCN)) gene identified 9 (8 known and 1 novel) variants. The prevalence of the known
deafness-associated 7511T>C, 7505T>C and 7445A>C mutations was 0.04%, 0.04% and 0.04%, respectively. Other variants were evaluated by the evolutionary conservation, allelic frequency of Chinese controls, potential structural and functional alterations and pedigree analysis. Three variants were polymorphisms, while the 7444G>A, 7471DelG and 7496A>G variants were putative
deafness-associated mutations. These putative
deafness-associated variants accounted for 0.68% cases of hearing-impaired subjects in this cohort. The low penetrance of
hearing loss in pedigrees carrying one of these putative
deafness-associated mutations indicated that the mutation(s) is necessary but itself insufficient to produce a clinical phenotype. Other genetic or environmental factor(s) may influence the phenotypic manifestation of these
tRNA(Ser(UCN)) mutations. Moreover, mtDNAs in 20 probands carrying one of the putative
deafness-associated mutations were widely dispersed among 8 Eastern Asian haplogroups. In particular, the occurrences of haplogroups D4a, M22, and H2 in patients carrying the
deafness-associated variants were higher than those in Chinese controls. These data further support that the mitochondrial
tRNA(Ser(UCN)) gene is the hot spot for mutations associated with
hearing loss. Thus, our findings may provide valuable information for the further understanding of pathophysiology and management of
hearing loss.