RT Journal Article
SR Electronic
T1 Mitochondrial mutations associated with aminoglycoside ototoxicity and hearing loss susceptibility identified by meta-analysis
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 95
OP 103
DO 10.1136/jmedgenet-2014-102753
VO 52
IS 2
A1 Jing, Wu
A1 Zongjie, Hao
A1 Denggang, Fu
A1 Na, Hei
A1 Bin, Zhang
A1 Aifen, Zhou
A1 Xijiang, Hu
A1 Cong, Yao
A1 Yunping, Dong
A1 Ring, Huijun Z
A1 Ring, Brian Z
YR 2015
UL http://jmg.bmj.com/content/52/2/95.abstract
AB Background Genetic variations, including mitochondrial mutations, are important contributors to hearing loss, especially in children, and newborn genetic screens for hearing loss mutations are becoming increasingly common. Mitochondrial mutations have been linked with ototoxic responses to common antibiotics, therefore understanding the association of these mutations with hearing loss is of special importance. To address the usefulness of screening for these mutations in a clinical setting, we formed a collaboration of clinicians and geneticists to analyse the association of mitochondrial mutations with non-syndromic hearing loss, including the effect of ethnicity, audiological test methods and aminoglycoside exposure. Methods This survey identified 122 variants in 43 studies that have been assessed for an association with hearing loss, and meta-analysis was performed on clinically relevant subsets. RNA folding and conservation analysis further explored possible relevance of these variants. Results Among all studies, eight variants were found to have significant associations with hearing loss. A partially overlapping set of six variants had significant association with hearing loss when aminoglycoside exposure was assessed. Five of these variants predictive of sensitivity to aminoglycoside spatially co-localise in an RNA folding model. There was little effect of the audiological test method used to assess hearing loss on the association with the variants. Conclusions Our results found a small set of studied variants had reproducible association with hearing loss, which will help clarify mutations useful in genetic screens for hearing loss. Several of the aminoglycoside exposure-associated mutations may co-localise on folded 12S rRNA, suggesting a functional association between these loci and aminoglycoside-induced hearing loss.