title: Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss.
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 approximately 13% and approximately 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 approximately 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.
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital and Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical College, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Li
authors.forename: Ronghua
authors.initials: R
authors.lastname: Li
authors.forename: Jianfu
authors.initials: J
authors.lastname: Chen
authors.forename: Zhisu
authors.initials: Z
authors.lastname: Liao
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yaping
authors.initials: Y
authors.lastname: Qian
authors.forename: Sudao
authors.initials: S
authors.lastname: Xiong
authors.forename: Selena
authors.initials: S
authors.lastname: Heman-Ackah
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wu
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Choo
authors.forename: Min-Xin
authors.initials: MX
authors.lastname: Guan
mesh_terms: D000293:Adolescent; D000617:Aminoglycosides / Q000378:metabolism*; D002648:Child; D002681:China; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008297:Male; D012335:RNA, Ribosomal / Q000235:genetics*
chemical_list: D000617:Aminoglycosides; D004272:DNA, Mitochondrial; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S