Postlingual hearing loss as a mitochondrial 3243A>G mutation phenotype

PLoS One. 2012;7(10):e44054. doi: 10.1371/journal.pone.0044054. Epub 2012 Oct 25.

Abstract

Background: The prevalence of isolated hearing loss (HL) associated with the m.3243A>G mutation is unknown. The aim of this study was to assess the frequency and heteroplasmy level of the m.3243A>G mutation in a large group of Polish patients with postlingual bilateral sensorineural HL of unidentified cause.

Methodology/principal findings: A molecular search was undertaken in the archival blood DNA of 1482 unrelated patients with isolated HL that had begun at ages between 5 and 40 years. Maternal relatives of the probands were subsequently investigated and all carriers underwent audiological tests. The m.3243A>G mutation was found in 16 of 1482 probands (an incidence of 1.08%) and 18 family members. Of these 34 individuals, hearing impairment was detected in 29 patients and the mean onset of HL was at 26 years. Some 42% of the identified m.3243A>G carriers did not develop multisystem symptomatology over the following 10 years. Mean heteroplasmy level of m.3243A>G was lowest in blood at a level of 14% and highest in urine at 58%. These values were independent of the manifested clinical severity of the disease.

Conclusions: A single m.3243A>G carrier can usually be found among each 100 individuals who have postlingual hearing loss of unknown cause. Urine samples are best for detecting the m.3243A>G mutation and diagnosing mitochondrially inherited hearing loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / chemistry
  • Adolescent
  • Adult
  • Age of Onset
  • Brain / pathology
  • DNA / analysis
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics
  • Female
  • Guanine / chemistry
  • Hearing Loss, Sensorineural / epidemiology
  • Hearing Loss, Sensorineural / genetics*
  • Heterozygote
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Mutation
  • Poland
  • Sex Factors

Substances

  • DNA, Mitochondrial
  • Guanine
  • DNA
  • Adenine

Grants and funding

The study was supported by grant from the Polish Ministry of Science and High Level Education NN 403 130 636, NN 407 118 939 and Polish mitochondrial network MITONET.pl. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No current external funding sources for this study.