A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness.
A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness.
复制标题
一种快速检测与氨基糖苷类引起的耳聋相关的五种已知突变的方法。
DOI：
10.1186/1471-2350-10-2
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发表时间：
2009-01-13
影响因子：
--
通讯作者：
de Jong, Greetje
中科院分区：
文献类型：
--
作者：
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
南非是世界上耐多药结核病（MDR-TB）发病率最高的国家之一。与此同时，氨基糖苷类抗生素在该国通常用作耐多药结核病的治疗。迄今为止，已知至少有五种突变会导致氨基糖苷类药物引起的听力损失。本研究的目的是开发一种快速筛查方法，以确定这些突变是否存在于南非人群中。采用SNaPshot技术的多重方法筛选MT-RNR 1基因的5个突变：A1555 G、C1494 T、T1095 C、961 delT +C（n）和A827 G。总共204个南非对照样品，包括98个混合血统和106个黑人个体，筛选了五种突变的存在。开发了一种稳健的、具有成本效益的方法，该方法可同时检测所有五种序列变体的存在。在该初步研究中，在黑人对照样品中以0.9%的频率鉴定出A1555 G突变。在6.6%的黑人对照和2%的混合血统对照中存在961 delT +C（n）变体。在所有研究参与者中均未发现T1095 C、C1494 T和A827 G变体。南非黑人人群中A1555 G突变的频率为0.9%，考虑到这一特定种族群体的耐多药结核病发病率很高，这一点令人担忧。未来更大规模的研究是必要的，以确定在一般南非人口的氨基糖苷类耳聋突变的真实频率。在对照组中观察到的961 delT +C（n）变异的高频率表明，这种变化是一种常见的非致病性多态性。这种遗传学方法有助于在氨基糖苷类药物治疗开始前识别听力损失的高风险个体。这在南非这样的低资源国家很重要，尽管有不良副作用，但氨基糖苷类药物仍将继续常规使用，并且伴随着非常有限的听力监测或没有听力监测。
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. 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. 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. 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.
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影响因子：
30.8
作者：
PREZANT, TR;AGAPIAN, JV;FISCHELGHODSIAN, N
通讯作者：
FISCHELGHODSIAN, N
影响因子：
4
作者：
VILJOEN, DL;SELLARS, SL;BEIGHTON, P
通讯作者：
BEIGHTON, P
影响因子：
5.3
作者：
Li, ZY;Li, RH;Guan, MX
通讯作者：
Guan, MX
影响因子：
3.7
作者：
Zager EM;McNerney R
通讯作者：
McNerney R
DOI：
10.1016/j.bbrc.2006.01.152
发表时间：
2006-04-07
影响因子：
3.1
作者：
Cassandrini, D;Calevo, MG;Bruno, C
通讯作者：
Bruno, C