Mutation analysis of mitochondrial 12S rRNA gene in Polish patients with non-syndromic and aminoglycoside-induced hearing loss
Mutation analysis of mitochondrial 12S rRNA gene in Polish patients with non-syndromic and aminoglycoside-induced hearing loss
复制标题
DOI：
10.1016/j.bbrc.2010.03.149
复制
发表时间：
2010-04-23
影响因子：
3.1
通讯作者：
Szyfter, Krzysztof
中科院分区：
文献类型：
--
作者：
Rydzanicz, Matgorzata;Wrobel, Maciej;Szyfter, Krzysztof
据报道，线粒体DNA突变与非综合征性和氨基糖苷性听力损失有关。在本研究中，我们对250例不相关的非综合征性氨基糖苷性听力损失患者进行了全12S rRNA基因突变筛查。共鉴定出21种不同的同质序列变异，包括8种常见多态性和1种耳聋相关突变m.1555一种>g和三种推定致病变异：m.669T > C, m.827A>G, m.961 δ +C(n)in。m.1555的发病率b> G估计为3.6% (9/250)；然而，当氨基糖苷暴露作为危险因素时，频率为5.5%（7/128）。替换m.669tb> C仅在听力受损和氨基糖苷暴露发作的患者中被发现，这可能表明这些额外的危险因素必须出现诱导临床表型。此外，两个12S rRNA序列变体：m.988G>A和m.1453定位于保守位点并影响RNA二级结构的>g可能是非综合征性和氨基糖苷诱导的听力损失相关突变的新候选者。(C) 2010爱思唯尔公司版权所有。
Mutations in mitochondrial DNA have been reported as associated with non-syndromic and aminoglycoside-induced hearing loss. In the present study, we have performed mutational screening of entire 12S rRNA gene in 250 unrelated patients with non-syndromic and aminoglycoside-induced hearing loss. Twenty-one different homoplasmic sequence variants were identified, including eight common polymorphisms, one deafness-associated mutation m.1555 A>G and three putatively pathogenic variants: m.669 T>C, m.827 A>G, m.961 delT+C(n)ins. The incidence of m.1555 A>G was estimated for 3.6% (9/250); however, where aminoglycoside exposure was taken as a risk factor, the frequency was 5.5% (7/128). Substitution m.669 T>C was identified only in patients with hearing impairment and episode of aminoglycoside exposure, which may suggest that such additional risk factors must appear to induce clinical phenotype. Moreover, two 12S rRNA sequence variants: m.988 G>A and m.1453 A>G, localized at conserved sites and affected RNA secondary structure, may be new candidates for non-syndromic and aminoglycoside-induced hearing loss associated mutations. (C) 2010 Elsevier Inc. All rights reserved.