title: Mitochondrial 12S rRNA variants in 1642 Han Chinese pediatric subjects with aminoglycoside-induced and nonsyndromic hearing loss.
abstract: In this report, we investigated the frequency and spectrum of mitochondrial 12S rRNA variants in a large cohort of 1642 Han Chinese pediatric subjects with aminoglycoside-induced and nonsyndromic hearing loss. Mutational analysis of 12S rRNA gene in these subjects identified 68 (54 known and 14 novel) variants. The frequencies of known 1555A>G and 1494C>T mutations were 3.96% and 0.18%, respectively, in this cohort with nonsyndromic and aminoglycoside-induced hearing loss. Prevalence of other putative deafness-associated mutation at positions 1095 and 961 were 0.61% and 1.7% in this cohort, respectively. Furthermore, the 745A>G, 792C>T, 801A>G, 839A>G, 856A>G, 1027A>G, 1192C>T, 1192C>A, 1310C>T, 1331A>G, 1374A>G and 1452T>C variants conferred increased sensitivity to ototoxic drugs or nonsyndromic deafness as they were absent in 449 Chinese controls and localized at highly conserved nucleotides of this rRNA. However, other variants appeared to be polymorphisms. Moreover, 65 Chinese subjects carrying the 1555A>G mutation exhibited bilateral and sensorineural hearing loss. A wide range of severity, age-of-onset and audiometric configuration was observed among these subjects. In particular, the sloping and flat-shaped patterns were the common audiograms in individuals carrying the 1555A>G mutation. The phenotypic variability in subjects carrying these 12S rRNA mutations indicated the involvement of nuclear modifier genes, mitochondrial haplotypes, epigenetic and environmental factors in the phenotypic manifestation of these mutations. Therefore, our data demonstrated that mitochondrial 12S rRNA is the hot spot for mutations associated with aminoglycoside ototoxicity.
authors.affiliation: Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lu
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Aifen
authors.initials: A
authors.lastname: Yang
authors.forename: Ronghua
authors.initials: R
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.forename: Qin
authors.initials: Q
authors.lastname: Cai
authors.forename: Guanghua
authors.initials: G
authors.lastname: Peng
authors.forename: Wuwei
authors.initials: W
authors.lastname: Zheng
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Tang
authors.forename: Bobei
authors.initials: B
authors.lastname: Chen
authors.forename: Jianfu
authors.initials: J
authors.lastname: Chen
authors.forename: Zhisu
authors.initials: Z
authors.lastname: Liao
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Li
authors.forename: Junyan
authors.initials: J
authors.lastname: You
authors.forename: Yu
authors.initials: Y
authors.lastname: Ding
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Jindan
authors.initials: J
authors.lastname: Wang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Sun
authors.forename: Jianyue
authors.initials: J
authors.lastname: Zhao
authors.forename: Ling
authors.initials: L
authors.lastname: Xue
authors.forename: Jiying
authors.initials: J
authors.lastname: Wang
authors.forename: Min-Xin
authors.initials: MX
authors.lastname: Guan
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000617:Aminoglycosides / Q000009:adverse effects* / Q000627:therapeutic use; D044466:Asian People; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D034381:Hearing Loss / Q000139:chemically induced* / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D017354:Point Mutation; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012335:RNA, Ribosomal / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D000617:Aminoglycosides; D000077278:RNA, Mitochondrial; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D012313:RNA