title: Unique penetrance of hearing loss in a five-generation Chinese family with the mitochondrial 12S rRNA 1555A > G mutation.
abstract: CONCLUSIONS
  Analysis of the complete mtDNA genome and X-linkage of this five-generation Chinese family revealed that the 1555A > G mutation may lead to deafness.
  
  
  OBJECTIVE
  Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. However, the variable clinical phenotype and incomplete penetrance of mtDNA 1555A > G-induced hearing loss complicate our understanding of this mutation. We aimed to identify whether nuclear genes, mitochondrial haplotypes/variants, and a possible threshold effect are involved in its manifestation in the pedigree.
  
  
  METHODS
  We performed clinical, genetic, and X-linkage analysis of a five-generation Chinese family in which all the affected individuals were male.
  
  
  RESULTS
  Clinical evaluation revealed that affected individuals with or without aminoglycoside exposure developed hearing loss extending gradually from 8000 Hz to 4000 Hz and then to 1000 Hz. Using X-linkage analysis and sequencing, we detected an identical homoplasmic 1555A > G mutation in nine individuals, and a previously unreported variant 14163C > T in mtDNA. The new variant 14163C > T coexisted with the 1555A > G mutation in six affected subjects of our pedigree. The previously unreported variant 14163C > T and aminoglycoside exposure may synergize the development of this deafness.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha City, Hunan Province, China.
authors.forename: Meichao
authors.initials: M
authors.lastname: Men
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.forename: Honghan
authors.initials: H
authors.lastname: Wang
authors.forename: Yalan
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
authors.forename: Chufeng
authors.initials: C
authors.lastname: He
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
mesh_terms: D000617:Aminoglycosides / Q000633:toxicity; D000900:Anti-Bacterial Agents / Q000633:toxicity; D044466:Asian People / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000139:chemically induced / Q000235:genetics*; D005260:Female; D050172:Genes, X-Linked / Q000235:genetics; D008040:Genetic Linkage; D014644:Genetic Variation / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D050809:POU Domain Factors / Q000235:genetics; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D012335:RNA, Ribosomal / Q000235:genetics*; D012729:Sex Chromosome Aberrations
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D017630:Connexins; D004272:DNA, Mitochondrial; D050809:POU Domain Factors; C091774:POU3F4 protein, human; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D000072259:Connexin 26