Mutation analysis of mitochondrial 12S rRNA gene in Polish patients with non-syndromic and aminoglycoside-induced hearing loss

Biochem Biophys Res Commun. 2010 Apr 23;395(1):116-21. doi: 10.1016/j.bbrc.2010.03.149. Epub 2010 Mar 28.

Abstract

Mutations in mitochondrial DNA have been reported as associated with non-syndromic and aminoglycoside-induced hearing loss. In the present study, we have performed mutational screening of entire 12S rRNA gene in 250 unrelated patients with non-syndromic and aminoglycoside-induced hearing loss. Twenty-one different homoplasmic sequence variants were identified, including eight common polymorphisms, one deafness-associated mutation m.1555 A>G and three putatively pathogenic variants: m.669 T>C, m.827 A>G, m.961 delT+C(n)ins. The incidence of m.1555 A>G was estimated for 3.6% (9/250); however, where aminoglycoside exposure was taken as a risk factor, the frequency was 5.5% (7/128). Substitution m.669 T>C was identified only in patients with hearing impairment and episode of aminoglycoside exposure, which may suggest that such additional risk factors must appear to induce clinical phenotype. Moreover, two 12S rRNA sequence variants: m.988 G>A and m.1453 A>G, localized at conserved sites and affected RNA secondary structure, may be new candidates for non-syndromic and aminoglycoside-induced hearing loss associated mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aminoglycosides / adverse effects*
  • Anti-Bacterial Agents / adverse effects*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Genes, Mitochondrial*
  • Genetic Testing
  • Hearing Loss / chemically induced*
  • Hearing Loss / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Pedigree
  • Poland
  • Polymorphism, Genetic
  • RNA, Ribosomal / genetics*
  • White People
  • Young Adult

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • RNA, Ribosomal
  • RNA, ribosomal, 12S