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BMJ Open 2:e001238 doi:10.1136/bmjopen-2012-001238
  • Ear, nose and throat/otolaryngology
    • Research

Prevalence and audiological features in carriers of GJB2 mutations, c.35delG and c.101T>C (p.M34T), in a UK population study

  1. Maria Bitner-Glindzicz4
  1. 1Centre for Hearing and Balance Studies, University of Bristol, Bristol, UK
  2. 2Department of Social and Community Medicine, University of Bristol, Bristol, UK
  3. 3Institute of Sound and Vibration Research, University of Southampton, Southampton, UK
  4. 4Institute of Child Health, UCL, London, UK
  1. Correspondence to Amanda Hall, Centre for Hearing and Balance Studies, 8-10 Berkeley Square, Bristol, BS8 1HH, UK; amanda.hall{at}bristol.ac.uk

  1. Contributors MP, MB-G and AH designed the study. AH took the lead in analysis, writing and submission. MP and MB-G provided genetics expertise. ML analysed the otoacoustic emission data and advised on audiological measures. CS advised on statistical analysis. All authors were involved in drafting, revising and agreeing the final version of the article.

  • Received 2 April 2012
  • Accepted 29 June 2012
  • Published 31 July 2012

Abstract

Objectives To determine the carrier rate of the GJB2 mutation c.35delG and c.101T>C in a UK population study; to determine whether carriers of the mutation had worse hearing or otoacoustic emissions compared to non-carriers.

Design Prospective cohort study.

Setting University of Bristol, UK.

Participants Children in the Avon Longitudinal Study of Parents and Children. 9202 were successfully genotyped for the c.35delG mutation and c.101>T and classified as either carriers or non-carriers.

Outcome measures Hearing thresholds at age 7, 9 and 11 years and otoacoustic emissions at age 9 and 11.

Results The carrier frequency of the c.35delG mutation was 1.36% (95% CI 1.13 to 1.62) and c.101T>C was 2.69% (95% CI 2.37 to 3.05). Carriers of c.35delG and c.101T>C had worse hearing than non-carriers at the extra-high frequency of 16 kHz. The mean difference in hearing at age 7 for the c.35delG mutation was 8.53 dB (95% CI 2.99, 14.07) and 12.57 dB at age 9 (95% CI 8.10, 17.04). The mean difference for c.101T>C at age 7 was 3.25 dB (95% CI −0.25 to 6.75) and 7.61 dB (95% CI 4.26 to 10.96) at age 9. Otoacoustic emissions were smaller in the c.35delG mutation carrier group: at 4 kHz the mean difference was −4.95 dB (95% CI −6.70 to −3.21) at age 9 and −3.94 dB (95% CI −5.78 to −2.10) at age 11. There was weak evidence for differences in otoacoustic emissions amplitude for c.101T>C carriers.

Conclusion Carriers of the c.35delG mutation and c.101T>C have worse extra-high-frequency hearing than non-carriers. This may be a predictor for changes in lower-frequency hearing in adulthood. The milder effects observed in carriers of c.101T>C are in keeping with its classification as a mutation causing mild/moderate hearing loss in homozygosity or compound heterozygosity.

Footnotes

  • Funding This research was specifically funded by Deafness Research UK. The UK Medical Research Council (Grant ref: 74882) the Wellcome Trust (Grant ref: 076467) and the University of Bristol provide core support for ALSPAC. MB-G is supported by Great Ormond Street Hospital Children's Charity.

  • Competing interests None.

  • Ethics approval ALSPAC Law and Ethics Committee and Local Research Ethics Committees.

  • Provenance and peer review Not commissioned; externally peer reviewed.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/3.0/ and http://creativecommons.org/licenses/by-nc/3.0/legalcode

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