Mitochondrial tRNAIle A4317G mutation may be associated with hearing impairment in a Han Chinese family

Mol Med Rep. 2018 Dec;18(6):5159-5165. doi: 10.3892/mmr.2018.9519. Epub 2018 Sep 27.

Abstract

Mutations in the mitochondrial genome have been identified to be associated with hearing loss. The aim of the present study was to investigate the role of mitochondrial DNA (mtDNA) variants in a Chinese family with hearing loss. Polymerase chain reaction (PCR)‑Sanger sequencing was used to screen the mtDNA variants and nuclear genes [gap junction protein β2 (GJB2) and transfer (t)RNA 5‑methylaminomethyle‑2‑thiouridylate methyltransferase (TRMU)]; in addition, the mtDNA copy number was determined by quantitative PCR. The present study characterized the molecular features of a Chinese family with maternally‑inherited hearing loss and identified mtDNA A1555G and tRNAIle A4317G mutations. The A4317G mutation was localized at the TΨC arm of tRNAIle (position 59) and created a novel base‑pairing (G59‑C54), which may alter the secondary structure of the tRNA. In addition, patients carrying the A4317G mutation exhibited a lower mtDNA copy number compared with the controls, suggesting that this mutation may cause mitochondrial dysfunction that is responsible for the deafness. However, no functional variants in the GJB2 and TRMU genes were detected. mtDNA A1555G and A4317G mutations may contribute to the clinical manifestation of hearing loss in this family.

MeSH terms

  • Adult
  • Asian People / genetics
  • China
  • Connexin 26
  • Connexins / genetics
  • DNA Copy Number Variations
  • DNA, Mitochondrial
  • Genes, Mitochondrial*
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genome, Mitochondrial
  • Genotype
  • Hearing Loss / diagnosis
  • Hearing Loss / genetics*
  • Humans
  • Middle Aged
  • Mitochondrial Proteins / genetics
  • Mutation*
  • Pedigree
  • Phenotype
  • Phylogeny
  • RNA, Transfer, Ile / chemistry
  • RNA, Transfer, Ile / genetics*
  • Severity of Illness Index
  • tRNA Methyltransferases / genetics

Substances

  • Connexins
  • DNA, Mitochondrial
  • GJB2 protein, human
  • Mitochondrial Proteins
  • RNA, Transfer, Ile
  • Connexin 26
  • tRNA Methyltransferases
  • TRMU protein, human