title: [Mitochondrial 12S rRNA variants studies in 456 subjects with hearing loss in seven schools for deaf and mutes in Zhejiang province].
abstract: OBJECTIVE
  To investigate mutational spectrum and frequency of the mitochondrial 12S rRNA gene in Chinese subjects with aminoglycoside-induced and non-syndromic hearing loss.
  
  
  METHODS
  Total of 456 subjects with non-syndromic hearing loss were recruited from seven schools for deaf-mutes in Zhejiang province. Genomic DNA was extracted from the whole blood, and then the DNA fragment was amplified spanning the 12S rRNA gene, followed by sequencing and analyzed.
  
  
  RESULTS
  Thirty-one variants were identified by mutation analysis of 12S rRNA gene in these subjects. The frequency of the known 1555A > G mutation was 4.4% (20/456). Prevalence of other putative deafness-associated mutation at positions 961 and 1095 were 2.0% (9/456) and 0.7% (3/456) respectively. Furthermore, the 1027A > G, 1109T > C and 1431G > A variants conferred increased sensitivity to ototoxic drugs or non-syndromic deafness as they were absent in 449 Chinese controls and localized at highly conserved nucleotides of this 12S rRNA gene. Moreover, clinical data showed a wide range of age-of-onset, variety of severity and various audiometric configurations in subjects carrying the 1555A > G mutation.
  
  
  CONCLUSIONS
  Our data demonstrated that the mitochondrial 12S rRNA gene is the hot spot for mutations associated with aminoglycoside ototoxicity and non-syndromic hearing loss. Nuclear modifier genes, mitochondrial haplotypes and environmental factors might play a role in the phenotypic manifestation of these mutations.
authors: Department of Otolaryngology, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical College, Wenzhou 325027, China.
authors: Guang-hua
authors: GH
authors: Peng
authors: Fang
authors: F
authors: Fang
authors: Jing
authors: J
authors: Zheng
authors: Bin-jiao
authors: BJ
authors: Zheng
authors: Xiao
authors: X
authors: Yu
authors: Yue
authors: Y
authors: Wu
authors: Ling-zhi
authors: LZ
authors: Liang
authors: Qiong-min
authors: QM
authors: Zhang
authors: Yi
authors: Y
authors: Zhu
authors: Xiao-wen
authors: XW
authors: Tang
authors: Bo-bei
authors: BB
authors: Chen
mesh_terms: D000293:Adolescent; D000617:Aminoglycosides / Q000235:genetics; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D009690:Nucleic Acid Conformation; D010375:Pedigree; D012335:RNA, Ribosomal / Q000235:genetics*; D055815:Young Adult
chemical_list: D000617:Aminoglycosides; D004272:DNA, Mitochondrial; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S