Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, Poland.
Biochem Biophys Res Commun. 2010 Apr 23;395(1):116-21. doi: 10.1016/j.bbrc.2010.03.149. Epub 2010 Mar 28.
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.
线粒体 DNA 突变与非综合征型和氨基糖苷类诱导的听力损失有关。在本研究中，我们对 250 名非综合征型和氨基糖苷类诱导的听力损失患者的整个 12S rRNA 基因进行了突变筛查。鉴定出 21 种不同的同质序列变异体，包括 8 种常见的多态性、1 种与耳聋相关的突变 m.1555 A>G 和 3 种可能的致病性变异体：m.669 T>C、m.827 A>G、m.961 delT+C(n)ins。m.1555 A>G 的发生率估计为 3.6%（250 例中有 9 例）；然而，当氨基糖苷类药物暴露被视为危险因素时，其频率为 5.5%（128 例中有 7 例）。替换 m.669 T>C 仅在听力受损和氨基糖苷类药物暴露的患者中被发现，这可能表明必须出现此类额外的危险因素才能诱导临床表型。此外，两种位于保守位点并影响 RNA 二级结构的 12S rRNA 序列变异体 m.988 G>A 和 m.1453 A>G 可能是非综合征型和氨基糖苷类诱导的听力损失相关突变的新候选者。
