title: A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Molecular Biology and Human Genetics, Stellenbosch University, Cape Town, South Africa. sbardien@sun.ac.za
authors.forename: Soraya
authors.initials: S
authors.lastname: Bardien
authors.forename: Hannique
authors.initials: H
authors.lastname: Human
authors.forename: Tashneem
authors.initials: T
authors.lastname: Harris
authors.forename: Gwynneth
authors.initials: G
authors.lastname: Hefke
authors.forename: Rene
authors.initials: R
authors.lastname: Veikondis
authors.forename: H Simon
authors.initials: HS
authors.lastname: Schaaf
authors.forename: Lize
authors.initials: L
authors.lastname: van der Merwe
authors.forename: John H
authors.initials: JH
authors.lastname: Greinwald
authors.forename: Johan
authors.initials: J
authors.lastname: Fagan
authors.forename: Greetje
authors.initials: G
authors.lastname: de Jong
mesh_terms: D000617:Aminoglycosides / Q000009:adverse effects* / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use; D044383:Black People; D004272:DNA, Mitochondrial / Q000235:genetics; D003638:Deafness / Q000139:chemically induced / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013019:South Africa; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy
chemical_list: D000617:Aminoglycosides; D000995:Antitubercular Agents; D004272:DNA, Mitochondrial