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?
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.
UCL Ear Institute, UCL, London, UK. Electronic address: g.al-malky@ucl.ac.uk.
Ghada
G
Al-Malky
Department of Paediatric Respiratory Medicine, Great Ormond Street Hospital and the Portex Unit, Institute of Child Health, UCL, London, UK.
Ranjan
R
Suri
Department of Audiology & Audiological Medicine, Great Ormond Street Hospital, London, UK.
Tony
T
Sirimanna
UCL Ear Institute, UCL, London, UK.
Sally J
SJ
Dawson
D000617:Aminoglycosides / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000235:genetics*; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006309:Hearing / Q000187:drug effects* / Q000235:genetics; D034381:Hearing Loss / Q000139:chemically induced / Q000235:genetics*; D006320:Hearing Tests; D006801:Humans; D019683:Penetrance; D010597:Pharmacogenetics; D017354:Point Mutation; D012335:RNA, Ribosomal / Q000235:genetics
D000617:Aminoglycosides; D004272:DNA, Mitochondrial; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S
12S rRNA gene; A1555G, m.1555A>G; Aminoglycosides; Cystic fibrosis; Hearing loss; Ototoxicity