The contribution of the mitochondrial COI/tRNA(Ser(UCN)) gene mutations to non-syndromic and aminoglycoside-induced hearing loss in Polish patients

Mol Genet Metab. Sep-Oct 2011;104(1-2):153-9. doi: 10.1016/j.ymgme.2011.05.004. Epub 2011 May 13.

Abstract

Mutations in mitochondrial DNA have been implicated in both, non-syndromic and aminoglycoside-induced hearing loss. In the present study, we have performed the systematic mutation screening of the COI/tRNA(Ser(UCN)) genes in 250 unrelated Polish subjects with hearing impairment. Three different homoplasmic sequence variants were identified, including one common polymorphism m.7476 C>T in tRNA(Ser(UCN)) and two mutations, m.7444 G>A and m.7445 A>G localized in the COI/precursor of tRNA(Ser(UCN)). The incidence of m.7444 G>A substitution was estimated at 1.6% (4/250), however variable penetrance of hearing loss, age of onset and hearing thresholds among m.7444 G>A carriers was observed. Two subjects had the positive history of aminoglycoside exposure and one of them harbored both m.7444 G>A and 12S rRNA m.1555 A>G mutations. Those suggest that m.7444 G>A itself is not sufficient to produce a clinical phenotype and additional modifier factors are required for pathogenic manifestation of m.7444 G>A substitution. Moreover, we have described the first Polish family with non-syndromic hearing loss, harboring m.7445 A>G mutation. The penetrance of hearing loss in this pedigree was 58% when aminoglycoside-induced hearing impairment was included, and 8% when ototoxic effect was excluded. This finding strongly suggests the possible role of m.7445 A>G in susceptibility to aminoglycoside induced-hearing loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides / adverse effects*
  • Audiometry
  • Base Sequence
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics
  • Electron Transport Complex IV / genetics*
  • Female
  • Hearing Loss, Sensorineural / chemically induced*
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Infant
  • Male
  • Mitochondria / enzymology*
  • Mitochondria / genetics
  • Molecular Sequence Data
  • Mutation / genetics*
  • Pedigree
  • Poland
  • RNA, Transfer, Ser / genetics*

Substances

  • Aminoglycosides
  • DNA, Mitochondrial
  • RNA, Transfer, Ser
  • Electron Transport Complex IV

Supplementary concepts

  • Nonsyndromic sensorineural hearing loss