Mitochondrial mutation associated with nonsyndromic deafness

Am J Otolaryngol. 1995 Nov-Dec;16(6):403-8. doi: 10.1016/0196-0709(95)90078-0.


Purpose: The first mutation associated with nonsyndromic deafness has recently been identified in pedigrees with susceptibility to aminoglycoside ototoxicity and in a large Arab-Israeli pedigree. The mutation is maternally transmitted, and is a nucleotide substitution in the mitochondrial 12S ribosomal RNA gene. A different sequence change, in the mitochondrial tRNA(Ser)(UCN)/COI gene, has been proposed as a candidate mutation in a Scottish nonsyndromic deafness pedigree. We have now identified a family in New Zealand with maternally inherited nonsyndromic sensorineural deafness, and the purpose of the current study is to identify the molecular basis of deafness in this family.

Materials and methods: A family tree was established by history and chart review, and audiological and clinical data were obtained. Blood was sampled from 10 family members, and lymphoblastoid cell lines were established for 4 of them. The DNA of these individuals was extracted, and the mitochondrial genome was analyzed by Southern blot analysis for gross rearrangements. Subsequently, the entire coding sequence of the mitochondrial genome was sequenced, compared to the normal sequence, and all sequence variations were analyzed by allele-specific oligonucleotide hybridization or restriction enzyme analysis.

Results: Several candidate mutations were identified, one of them being the nucleotide 7445 A-->G mutation in the mitochondrial tRNAser(UCN)/COI gene. This mutation was heteroplasmic and identical to the one previously identified in the Scottish pedigree.

Conclusions: The finding of the same heteroplasmic mutation in two independent pedigrees with the same phenotype and transmission pattern, establishes this sequence change as the most likely determinant of the deafness phenotype in these families. This implies that nonsyndromic deafness can be caused by mutations in generalized cell processes, such as oxidative phosphorylation, rather than in hearing specific molecules.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Base Sequence
  • Child
  • Child, Preschool
  • DNA / genetics
  • Deafness / genetics*
  • Disease Susceptibility
  • Female
  • Gene Rearrangement
  • Genome, Human
  • Humans
  • Infant
  • Male
  • Mitochondria / genetics*
  • Mutation / genetics*
  • New Zealand
  • Oxidative Phosphorylation
  • Pedigree
  • Phenotype
  • RNA, Ribosomal / genetics
  • RNA, Transfer, Ser / genetics
  • Retrospective Studies
  • Scotland
  • X Chromosome


  • RNA, Ribosomal
  • RNA, Transfer, Ser
  • RNA, ribosomal, 12S
  • DNA