Browsing by Author "Bardien, Soraya"

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    Aminoglycoside-induced hearing loss: South Africans at risk
    (2009) Bardien, Soraya; de Jong, Greetje; Schaaf, H Simon; Harris, Tashneem; Fagan, Johan; Petersen, Lucretia
    South Africa is currently experiencing a TB epidemic with an estimated incidence of 940/100 000 population/year, and the country has been ranked 4th among the 22 high-burden TB countries worldwide by the World Health Organization (WHO). A potentially devastating threat to TB control is the emergence of multidrug-resistant TB (MDR-TB) and, more recently, extensively drug-resistant TB (XDR-TB), mainly as a result of poor drug adherence by TB patients and incorrect management or treatment regimens by health providers; however, direct transmission of drug-resistant strains also plays an important role. The MDR/XDR-TB strains necessitate prolonged chemotherapy for up to 2 years or more, and the use of more toxic second-line drugs including the aminoglycoside (streptomycin, kanamycin and amikacin) and polypeptide (capreomycin) antibiotics. In South Africa, in accordance with WHO guidelines, streptomycin is used for retreatment of TB while kanamycin, amikacin and capreomycin are used to treat MDR/XDR-TB.
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    Arrhythmogenic right ventricular cardiomyopathy type 6 (ARVC6): support for the locus assignment, narrowing of the critical region and mutation screening of three candidate genes
    (BioMed Central Ltd, 2006) Matolweni, Luzuko; Bardien, Soraya; Rebello, George; Oppon, Ekow; Munclinger, Miroslav; Ramesar, Rajkumar; Watkins, Hugh; Mayosi, Bongani
    BACKGROUND:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable disorder characterized by progressive degeneration of right ventricular myocardium, arrhythmias and an increased risk of sudden death at a young age. By linkage analysis, ARVC type 6 was previously mapped to a 10.6 cM region on chromosome 10p12-p14 in a large North American kindred. To date, the genetic defect that causes ARVC6 has not been identified. METHODS: We identified a South African family of 13 members with ARVC segregating as an autosomal dominant disorder. The diagnosis of ARVC was based on international diagnostic criteria. All available family members were genotyped with microsatellite markers at six known ARVC loci, and positional candidate gene screening was performed. RESULTS: Genetic linkage and haplotype analysis provided lod scores that are highly suggestive of linkage to the ARVC6 locus on chromosome 10p12-p14, and the narrowing of the critical region to ~2.9 Mb. Two positional candidate genes (ITG8 and FRMD4A) were screened in which defects could possibly disrupt cell-cell adhesion. A non-positional candidate gene with apoptosis inducing properties, LAMR1P6 (laminin receptor 1 pseudogene 6) was also screened. Direct sequencing of DNA from affected individuals failed to detect disease-causing mutations in the exonic sequences of the three genes investigated. CONCLUSION: The narrowing of the ARVC6 critical region may facilitate progress towards the identification of the gene that is involved in ARVC. Identification of the causative genes for ARVC will contribute to the understanding of the pathogenesis and management of this poorly understood condition.
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    A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness
    (BioMed Central Ltd, 2009) Bardien, Soraya; Human, Hannique; Harris, Tashneem; Hefke, Gwynneth; Veikondis, Rene; Schaaf, H Simon; van der Merwe, Lize; Greinwald, John; Fagan, Johan; de Jong, Greetje
    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.