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

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dc.contributor.authorBardien, Sorayaen_ZA
dc.contributor.authorHuman, Hanniqueen_ZA
dc.contributor.authorHarris, Tashneemen_ZA
dc.contributor.authorHefke, Gwynnethen_ZA
dc.contributor.authorVeikondis, Reneen_ZA
dc.contributor.authorSchaaf, H Simonen_ZA
dc.contributor.authorvan der Merwe, Lizeen_ZA
dc.contributor.authorGreinwald, Johnen_ZA
dc.contributor.authorFagan, Johanen_ZA
dc.contributor.authorde Jong, Greetjeen_ZA
dc.date.accessioned2015-10-28T06:56:37Z
dc.date.available2015-10-28T06:56:37Z
dc.date.issued2009en_ZA
dc.description.abstractBACKGROUND: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.en_ZA
dc.identifier.apacitationBardien, S., Human, H., Harris, T., Hefke, G., Veikondis, R., Schaaf, H. S., ... de Jong, G. (2009). A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness. <i>BMC Medical Genetics</i>, http://hdl.handle.net/11427/14445en_ZA
dc.identifier.chicagocitationBardien, Soraya, Hannique Human, Tashneem Harris, Gwynneth Hefke, Rene Veikondis, H Simon Schaaf, Lize van der Merwe, John Greinwald, Johan Fagan, and Greetje de Jong "A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness." <i>BMC Medical Genetics</i> (2009) http://hdl.handle.net/11427/14445en_ZA
dc.identifier.citationBardien, S., et al. (2009). A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness. BMC Medical Genetics, 10(1), 2.en_ZA
dc.identifier.ris TY - Journal Article AU - Bardien, Soraya AU - Human, Hannique AU - Harris, Tashneem AU - Hefke, Gwynneth AU - Veikondis, Rene AU - Schaaf, H Simon AU - van der Merwe, Lize AU - Greinwald, John AU - Fagan, Johan AU - de Jong, Greetje AB - 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. DA - 2009 DB - OpenUCT DO - 10.1186/1471-2350-10-2 DP - University of Cape Town J1 - BMC Medical Genetics LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness TI - A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness UR - http://hdl.handle.net/11427/14445 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14445
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2350-10-2
dc.identifier.vancouvercitationBardien S, Human H, Harris T, Hefke G, Veikondis R, Schaaf HS, et al. A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness. BMC Medical Genetics. 2009; http://hdl.handle.net/11427/14445.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentDivision of Otorhinolaryngologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2009 Bardien et al; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceBMC Medical Geneticsen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcmedgenet/en_ZA
dc.subject.otherAminoglycosidesen_ZA
dc.subject.otherAntitubercular Agentsen_ZA
dc.subject.otherDeafnessen_ZA
dc.subject.otherDNA, Mitochondrialen_ZA
dc.subject.otherSequence Analysis, DNAen_ZA
dc.subject.otherTuberculosis, Multidrug-Resistanten_ZA
dc.titleA rapid method for detection of five known mutations associated with aminoglycoside-induced deafnessen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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