Y Ding, B-H Xia, Y-S Teng, G-C Zhuo, J-H Leng
Central Laboratory, Hangzhou First People's Hospital, Hangzhou, People's Republic of China.
Affiliated Hangzhou Hospital, Nanjing Medical University, Hangzhou, People's Republic of China.
Balkan J Med Genet. 2017 Dec 29;20(2):43-50. doi: 10.1515/bjmg-2017-0025. eCollection 2017 Dec.
Variations in mitochondrial genome have been found to be associated with hearing loss. Of these, the mitochondrial 12S rRNA and tRNA are the hot-spots for pathogenic variants associated with deafness. To understand the putative role of mitochondrial DNA (mtDNA) variants in hearing loss, we recently screened the variants in mitochondrial genomes in patients with deafness from the Hangzhou area of Zhejiang Province, People's Republic of China (PRC). In this study, we describe a maternally-inherited Han Chinese family with high penetrance of hearing loss, notably, the penetrance of hearing loss in this family were 80.0 and 40.0%, when the aminoglycoside was included or excluded. Three matrilineal relatives in this pedigree exhibited different levels of hearing loss with different age at onset. In addition, sequence analysis of the complete mitochondrial genome showed the presence of the well-known C1494T pathogenic variant in the gene and the G7444A pathogenic variant in the COI/ tRNA. The C1494T anomaly had been reported to be a pathogenic mutation associated with aminoglycoside-induced and nonsyndromic hearing loss (AINHL), while the G7444A was considered as a secondary mutation associated with deafness. However, the lack of functional variants in and genes suggested that nuclear modified genes may not play important roles in deafness expression. Thus, the combination of G7444A and C1494T pathogenic variants in the mitochondrial genome may account for the high penetrance of hearing loss in this Chinese family.
线粒体基因组变异已被发现与听力损失有关。其中，线粒体12S rRNA和tRNA是与耳聋相关的致病变异热点。为了解线粒体DNA（mtDNA）变异在听力损失中的假定作用，我们最近对来自中华人民共和国浙江省杭州地区的耳聋患者的线粒体基因组变异进行了筛查。在本研究中，我们描述了一个母系遗传的汉族家庭，其听力损失具有高外显率，值得注意的是，当包含或排除氨基糖苷类药物时，该家庭听力损失的外显率分别为80.0%和40.0%。该家系中的三名母系亲属表现出不同程度的听力损失，发病年龄也不同。此外，对完整线粒体基因组的序列分析显示，在该基因中存在著名的C1494T致病变异，在COI/tRNA中存在G7444A致病变异。据报道，C1494T异常是与氨基糖苷类药物诱导的非综合征性听力损失（AINHL）相关的致病突变，而G7444A被认为是与耳聋相关的继发突变。然而，该基因和该基因中缺乏功能性变异表明，核修饰基因可能在耳聋表达中不发挥重要作用。因此，线粒体基因组中G7444A和C1494T致病变异的组合可能是这个中国家庭听力损失高外显率的原因。
