A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness

Bardien, Soraya
Human, Hannique
Harris, Tashneem
Hefke, Gwynneth
Veikondis, Rene
Schaaf, H. Simon
Van der Merwe, Lize
Greinwald, John H.
Fagan, Johan
De Jong, Greetje
Journal Title
Journal ISSN
Volume Title
BioMed Central
Background: South Africa has one of the highest incidences of multidrug-resistant tuberculosis (MDR-TB) in the world. Concomitantly, aminoglycosides are commonly used in this country as a treatment against MDR-TB. To date, at least five mutations are known to confer susceptibility to aminoglycoside-induced hearing loss. The aim of the present study was to develop a rapid screening method to determine whether these mutations are present in the South African population. Methods: A multiplex method using the SNaPshot technique was used to screen for five mutations in the MT-RNR1 gene: A1555G, C1494T, T1095C, 961delT+C(n) and A827G. A total of 204 South African control samples, comprising 98 Mixed ancestry and 106 Black individuals were screened for the presence of the five mutations. Results: A robust, cost-effective method was developed that detected the presence of all five sequence variants simultaneously. In this pilot study, the A1555G mutation was identified at a frequency of 0.9% in the Black control samples. The 961delT+C(n) variant was present in 6.6% of the Black controls and 2% of the Mixed ancestry controls. The T1095C, C1494T and A827G variants were not identified in any of the study participants. Conclusion: The frequency of 0.9% for the A1555G mutation in the Black population in South Africa is of concern given the high incidence of MDR-TB in this particular ethnic group. Future larger studies are warranted to determine the true frequencies of the aminoglycoside deafness mutations in the general South African population. The high frequencies of the 961delT+C(n) variant observed in the controls suggest that this change is a common non-pathogenic polymorphism. This genetic method facilitates the identification of individuals at high risk of developing hearing loss prior to the start of aminoglycoside therapy. This is important in a low-resource country like South Africa where, despite their adverse side-effects, aminoglycosides will continue to be used routinely and are accompanied with very limited or no audiological monitoring.
Multidrug-resistant tuberculosis (MDR-TB), Aminoglycosides mutations, Aminoglycoside-induced hearing loss, SNaPshot technique
Bardien, S, Human, H, Harris, T, Hefke, G, Veikondis, R, Schaaf, HS, Van der Merwe, L, Greinwald, JH, Fagan, J & De Jong, G 2009. 'A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness', BMC Medical Genetics, 10(1):2.