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Hearing in 44-45 year olds with m.1555A > G, a genetic mutation predisposing to aminoglycoside-induced deafness: a population based cohort study.

Rahman, S; Ecob, R; Costello, H; Sweeney, MG; Duncan, AJ; Pearce, K; Strachan, D; Forge, A; Davis, A; Bitner-Glindzicz, M (2012) Hearing in 44-45 year olds with m.1555A > G, a genetic mutation predisposing to aminoglycoside-induced deafness: a population based cohort study. BMJ OPEN, 2 (e000411). -. ISSN 2044-6055 https://doi.org/10.1136/bmjopen-2011-000411
SGUL Authors: Strachan, David Peter

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Abstract

Background The mitochondrial DNA mutation m.1555A>G predisposes to permanent idiosyncratic aminoglycoside-induced deafness that is independent of dose. Research suggests that in some families, m.1555A>G may cause non-syndromic deafness, without aminoglycoside exposure, as well as reduced hearing thresholds with age (age-related hearing loss). Objectives To determine whether adults with m.1555A>G have impaired hearing, a factor that would inform the cost-benefit argument for genetic testing prior to aminoglycoside administration. Design Population-based cohort study. Setting UK. Participants Individuals from the British 1958 birth cohort. Measurements Hearing thresholds at 1 and 4 kHz at age 44-45 years; m.1555A>G genotyping. Results 19 of 7350 individuals successfully genotyped had the m.1555A>G mutation, giving a prevalence of 0.26% (95% CI 0.14% to 0.38%) or 1 in 385 (95% CI 1 in 714 to 1 in 263). There was no significant difference in hearing thresholds between those with and without the mutation. Single-nucleotide polymorphism analysis indicated that the mutation has arisen on a number of different mitochondrial haplogroups. Limitations No data were collected on aminoglycoside exposure. For three subjects, hearing thresholds could not be predicted because information required for modelling was missing. Conclusions In this cohort, hearing in those with m.1555A>G is not significantly different from the general population and appears to be preserved at least until 44-45 years of age. Unbiased ascertainment of mutation carriers provides no evidence that this mutation alone causes non-syndromic hearing impairment in the UK. The findings lend weight to arguments for genetic testing for this mutation prior to aminoglycoside administration, as hearing in susceptible individuals is expected to be preserved well into adult life. Since global use of aminoglycosides is likely to increase, development of a rapid test is a priority.

Item Type: Article
Additional Information: © 2012, Published by the BMJ Publishing Group Limited. 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.
Keywords: Science & Technology, Life Sciences & Biomedicine, Medicine, General & Internal, General & Internal Medicine, MITOCHONDRIAL 1555A-GREATER-THAN-G MUTATION, RIBOSOMAL-RNA MUTATION, PREVALENCE, ANTIBIOTICS, OTOTOXICITY, CELLS, MTDNA
SGUL Research Institute / Research Centre: Academic Structure > Population Health Research Institute (INPH)
Journal or Publication Title: BMJ OPEN
ISSN: 2044-6055
Dates:
DateEvent
5 January 2012Published
PubMed ID: 22223843
Web of Science ID: 22223843
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URI: https://openaccess.sgul.ac.uk/id/eprint/157
Publisher's version: https://doi.org/10.1136/bmjopen-2011-000411

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