Normal hearing in a child with the m.1555A>G mutation despite repeated exposure to aminoglycosides. Has the penetrance of this pharmacogenetic interaction been overestimated?

Abstract The mtDNA m.1555A>G mutation causes increased susceptibility to aminoglycoside ototoxicity resulting in significant hearing loss in 100% of reported exposed cases. Genetic and audiological assessments were conducted in a sample of 59 children with cystic fibrosis (CF) undergoing aminogly...

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Bibliographic Details
Published in:International journal of pediatric otorhinolaryngology 2014-06, Vol.78 (6), p.969-973
Main Authors: Al-Malky, Ghada, Suri, Ranjan, Sirimanna, Tony, Dawson, Sally J
Format: Article
Language:English
Subjects:
12S rRNA gene
A1555G, m.1555A>G
Aminoglycosides
Aminoglycosides - adverse effects
Child
Child, Preschool
Cystic fibrosis
Cystic Fibrosis - drug therapy
Cystic Fibrosis - genetics
DNA Mutational Analysis
DNA, Mitochondrial - genetics
Female
Hearing - drug effects
Hearing - genetics
Hearing loss
Hearing Loss - chemically induced
Hearing Loss - genetics
Hearing Tests
Humans
Otolaryngology
Ototoxicity
Pediatrics
Penetrance
Pharmacogenetics
Point Mutation
RNA, Ribosomal - genetics
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Summary:Abstract The mtDNA m.1555A>G mutation causes increased susceptibility to aminoglycoside ototoxicity resulting in significant hearing loss in 100% of reported exposed cases. Genetic and audiological assessments were conducted in a sample of 59 children with cystic fibrosis (CF) undergoing aminoglycoside treatment. Of the two m.1555G patients identified one had severe-profound deafness. Surprisingly, the second m.1555G patient exhibited well-preserved hearing despite repeated exposure. This may be a rare case of intact hearing in an m.1555G individual with aminoglycoside use. Alternatively, its penetrance may have been previously overestimated due to recruitment bias. Further studies are required to determine the true penetrance to inform m.1555A>G genetic testing in similar clinical scenarios.
ISSN:0165-5876
1872-8464
DOI:10.1016/j.ijporl.2014.02.015