title: Systematic analysis of mitochondrial genes associated with hearing loss in the Japanese population: dHPLC reveals a new candidate mutation.
abstract: BACKGROUND
  Variants of mitochondrial DNA (mtDNA) have been evaluated for their association with hearing loss. Although ethnic background affects the spectrum of mtDNA variants, systematic mutational analysis of mtDNA in Japanese patients with hearing loss has not been reported.
  
  
  METHODS
  Using denaturing high-performance liquid chromatography combined with direct sequencing and cloning-sequencing, Japanese patients with prelingual (N = 54) or postlingual (N = 80) sensorineural hearing loss not having pathogenic mutations of m.1555A > G and m.3243A > G nor GJB2 were subjected to mutational analysis of mtDNA genes (12S rRNA, tRNALeu(UUR), tRNASer(UCN), tRNALys, tRNAHis, tRNASer(AGY), and tRNAGlu).
  
  
  RESULTS
  We discovered 15 variants in 12S rRNA and one homoplasmic m.7501A > G variant in tRNASer(UCN); no variants were detected in the other genes. Two criteria, namely the low frequency in the controls and the high conservation among animals, selected the m.904C > T and the m.1105T > C variants in 12S rRNA as candidate pathogenic mutations. Alterations in the secondary structures of the two variant transcripts as well as that of m.7501A > G in tRNASer(UCN) were predicted.
  
  
  CONCLUSIONS
  The m.904C > T variant was found to be a new candidate mutation associated with hearing loss. The m.1105T > C variant is unlikely to be pathogenic. The pathogenicity of the homoplasmic m.7501T > A variant awaits further study.
authors: Laboratory of Auditory Disorders, Division of Hearing and Balance Research, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan.
authors: Hideki
authors: H
authors: Mutai
authors: Hiroko
authors: H
authors: Kouike
authors: Eiko
authors: E
authors: Teruya
authors: Ikuko
authors: I
authors: Takahashi-Kodomari
authors: Hiroki
authors: H
authors: Kakishima
authors: Hidenobu
authors: H
authors: Taiji
authors: Shin-ichi
authors: S
authors: Usami
authors: Torayuki
authors: T
authors: Okuyama
authors: Tatsuo
authors: T
authors: Matsunaga
mesh_terms: D002851:Chromatography, High Pressure Liquid; D000072259:Connexin 26; D017630:Connexins; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010375:Pedigree
chemical_list: D017630:Connexins; D004272:DNA, Mitochondrial; C000607042:GJB2 protein, human; D000072259:Connexin 26