Abstract
The vestibular and ototoxic effects of the aminoglycoside antibiotics (streptomycin, gentamycin, kanamycin, tobramycin, neomycin) are well known; streptomycin, in particular, has been found to cause irreversible, profound, high frequency sensorineural deafness in hypersensitive persons. Aminoglycoside ototoxicity occurs both sporadically and within families and has been associated with a mitochondrial DNA (mtDNA) 1555A to G point mutation in the 12S ribosomal RNA gene. We report on the molecular analysis of a South African family with streptomycin induced sensorineural deafness in which we have found transmission of this same predisposing mutation. It is now possible to identify people who are at risk of hearing loss if treated with aminoglycosides in the future and to counsel them accordingly. In view of the fact that aminoglycoside antibiotics remain in widespread use for the treatment of infections, in particular for tuberculosis, which is currently of epidemic proportions in South Africa, this finding has important implications for the family concerned. In addition, other South African families may potentially be at risk if they carry the same mutation.
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- Cortopassi G., Hutchin T. A molecular and cellular hypothesis for aminoglycoside-induced deafness. Hear Res. 1994 Jul;78(1):27–30. doi: 10.1016/0378-5955(94)90040-x. [DOI] [PubMed] [Google Scholar]
- Higashi K. Unique inheritance of streptomycin-induced deafness. Clin Genet. 1989 Jun;35(6):433–436. [PubMed] [Google Scholar]
- Hu D. N., Qui W. Q., Wu B. T., Fang L. Z., Zhou F., Gu Y. P., Zhang Q. H., Yan J. H., Ding Y. Q., Wong H. Genetic aspects of antibiotic induced deafness: mitochondrial inheritance. J Med Genet. 1991 Feb;28(2):79–83. doi: 10.1136/jmg.28.2.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hutchin T. P., Cortopassi G. A. Multiple origins of a mitochondrial mutation conferring deafness. Genetics. 1997 Mar;145(3):771–776. doi: 10.1093/genetics/145.3.771. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hutchin T., Haworth I., Higashi K., Fischel-Ghodsian N., Stoneking M., Saha N., Arnos C., Cortopassi G. A molecular basis for human hypersensitivity to aminoglycoside antibiotics. Nucleic Acids Res. 1993 Sep 11;21(18):4174–4179. doi: 10.1093/nar/21.18.4174. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jaber L., Shohat M., Bu X., Fischel-Ghodsian N., Yang H. Y., Wang S. J., Rotter J. I. Sensorineural deafness inherited as a tissue specific mitochondrial disorder. J Med Genet. 1992 Feb;29(2):86–90. doi: 10.1136/jmg.29.2.86. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matthijs G., Claes S., Longo-Mbenza B., Cassiman J. J. Non-syndromic deafness associated with a mutation and a polymorphism in the mitochondrial 12S ribosomal RNA gene in a large Zairean pedigree. Eur J Hum Genet. 1996;4(1):46–51. doi: 10.1159/000472169. [DOI] [PubMed] [Google Scholar]
- Prezant T. R., Agapian J. V., Bohlman M. C., Bu X., Oztas S., Qiu W. Q., Arnos K. S., Cortopassi G. A., Jaber L., Rotter J. I. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nat Genet. 1993 Jul;4(3):289–294. doi: 10.1038/ng0793-289. [DOI] [PubMed] [Google Scholar]
- Sellars S., Beighton P. Childhood deafness in southern Africa. An aetiological survey of 3,064 deaf children. J Laryngol Otol. 1983 Oct;97(10):885–889. doi: 10.1017/s0022215100095736. [DOI] [PubMed] [Google Scholar]
- Viljoen D. L., Sellars S. L., Beighton P. Familial aggregation of streptomycin ototoxicity: autosomal dominant inheritance? J Med Genet. 1983 Oct;20(5):357–360. doi: 10.1136/jmg.20.5.357. [DOI] [PMC free article] [PubMed] [Google Scholar]