Novel mitochondrial gene variants in Northwestern Chinese probands with non-syndromic hearing loss by whole mitochondrial genome screening
Novel mitochondrial gene variants in Northwestern Chinese probands with non-syndromic hearing loss by whole mitochondrial genome screening
复制标题
通过全线粒体基因组筛查发现中国西北非综合征性听力损失先证者线粒体基因新变异
DOI：
10.1016/j.gene.2018.01.098
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发表时间：
2018-04-30
期刊：
影响因子：
3.5
通讯作者：
Guo, YuFen
中科院分区：
文献类型：
--
作者：
Chen, Xiaowan;Wang, Fang;Guo, YuFen
线粒体DNA突变在遗传性听力损失中起重要作用。本研究旨在鉴定更多新的线粒体DNA遗传变异。对97例中国西北地区非综合征性耳聋先证者和376例对照者进行线粒体全基因组检测。使用以下标准评估变体的致病性：（1）存在于< 1%的对照中，（2）进化保守性，（3）潜在的结构和功能改变。先证者的突变分析鉴定出706个变异，其中D环区变异180个，12S rRNA基因变异27个，16S rRNA基因变异29个，蛋白质编码区错义变异122个，沉默变异312个，tRNA基因变异29个，非编码区变异7个。在进一步分析评估潜在的结构和功能意义后，我们确定了5个新的听力损失候选变体：12S rRNA 1473C> T，tRNA（Phe）614A > C，tRNA（LYs）8339A > G，ND1 3866T > C和非编码5656A > G。本研究为进一步了解这些基因在中国人听力损失发生中的作用提供了有价值的信息。
Mitochondrial DNA mutations play an important role in hereditary hearing loss. The present study aimed at identifying more novel genetic variants of mitochondrial DNA. Complete Mitochondrial genomes were detected in 97 Northwestern Chinese probands with non-syndromic hearing loss and 376 control subjects. The variants were evaluated for the pathogenicity using the following criteria: (1) present in < 1% of the controls, (2) evolutional conservation, (3) potential structural and functional alterations. Mutational analysis in probands identified 706 variants, including 180 variants in the D loop region, 27 variants in the 12S rRNA gene, 29 variants in the 16S rRNA gene, 122 missense variants and 312 silent variants in the protein coding gene, 29 variants in the tRNA genes and 7 variants in the non-coding region. After further analysis assessed for the potential structural and functional significance, we identified 5 new candidate variants for hearing loss: 12S rRNA1473C > T, tRNA(Phe) 614A > C, tRNA(LYs) 8339A > G, ND1 3866T > C and non-coding 5656A > G. Our findings may provide the role of these genes in hearing loss development in China and valuable information for the further understanding of pathogenic mechanism of hearing loss.