title: Maternally transmitted aminoglycoside-induced and non-syndromic hearing loss caused by the 1494C > T mutation in the mitochondrial 12S rRNA gene in two Chinese families.
abstract: OBJECTIVE
  To explore the molecular genetic characterization of two Chinese families with aminoglycoside-induced and non-syndromic hearing loss (NSHL).
  
  
  METHODS
  Clinical evaluations, sequence analysis of mitochondrial DNA (mtDNA) as well as two nuclear genes TRMU and MTO1 encoding mitochondrial proteins.
  
  
  METHODS
  Two Chinese families with aminoglycoside-induced and NSHL.
  
  
  RESULTS
  Clinical evaluations revealed incomplete penetrance (28.6% vs. 40.0%) and variable phenotype of hearing losses between two families. When the effect of aminoglycosides was excluded, the penetrances were both 0%. Sequence analysis of mitochondrial genomes showed a homoplasmic 1494C > T mutation in the12S rRNA gene (MT-RNR1) in all maternal relatives, as well as distinct sets of mtDNA polymorphism belonging to Eastern Asian haplogroups D4j and D5a2, respectively. However, none of these mtDNA variants was highly evolutionarily conserved and implicated to have functional significance. No mutations were identified in either TRMU or MTO1 gene.
  
  
  CONCLUSIONS
  Mitochondrial 1494C> T mutation is the molecular basis responsible for the NSHL of two families, and the use of aminoglycoside antibiotics can worsen the hearing of the mutation carriers. Our results indicate the importance of a systematic screening for the mitochondrial 1494C > T mutation in Chinese subjects in the prevention of aminoglycoside-induced and non-syndromic hearing loss.
authors.affiliation: Department of Biotechnology, Nanjing Medical University, Nanjing, China.
authors.forename: Qinjun
authors.initials: Q
authors.lastname: Wei
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Chen
authors.forename: Haifeng
authors.initials: H
authors.lastname: Li
authors.forename: Yajie
authors.initials: Y
authors.lastname: Lu
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.forename: Xingkuan
authors.initials: X
authors.lastname: Bu
authors.forename: Guangqian
authors.initials: G
authors.lastname: Xing
authors.forename: Xin
authors.initials: X
authors.lastname: Cao
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D000617:Aminoglycosides / Q000009:adverse effects*; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics*; D001299:Audiometry; D001309:Auditory Threshold; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006309:Hearing / Q000187:drug effects / Q000235:genetics; D034381:Hearing Loss / Q000139:chemically induced* / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D040941:Heredity; D006801:Humans; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D019683:Penetrance; D012335:RNA, Ribosomal / Q000235:genetics*; D016601:RNA-Binding Proteins; D012359:tRNA Methyltransferases / Q000235:genetics
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D004272:DNA, Mitochondrial; C492006:MTO1 protein, human; D024101:Mitochondrial Proteins; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D016601:RNA-Binding Proteins; D012359:tRNA Methyltransferases; C496706:TRMU protein, human