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?

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• 作者：Ghada Al-Malky^a ; ^{g.al-malky@ucl.ac.uk" class="auth_mail} ; Ranjan Suri^b ; Tony Sirimanna^c ; Sally J. Dawson^a
• 关键词：Cystic fibrosis ; A1555G ; m.1555A> ; G ; 12S rRNA gene ; Ototoxicity ; Hearing loss ; Aminoglycosides
• 刊名：International Journal of Pediatric Otorhinolaryngology
• 出版年：June 2014
• 年：2014
• 卷：78
• 期：6
• 页码：969-973
• 全文大小：635 K

文摘

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.