Jacobs H T
Institute of Medical Technology, University of Tampere, Finland.
Ann Med. 1997 Dec;29(6):483-91. doi: 10.3109/07853899709007472.
Hearing impairment is a common disorder, largely genetic in origin, and showing classical features of a heterogeneous genetic disease. Up to 100 independently acting nuclear genes are involved in the disorder, of which around 30 have been mapped, but only a handful identified. Mutations in mitochondrial DNA also play a significant role in both syndromic and nonsyndromic sensorineural hearing impairment. Environmental agents such as aminoglycoside antibiotics and as yet unidentified nuclear genes interact with mitochondrial mutations in the expression of auditory phenotypes. The spectrum of different mitochondrial mutations associated with hearing impairment, taken together with mechanistic studies at the molecular level, suggests that the pathogenic process involves the accumulation of abnormal translation products inside mitochondria, in sensitive cells of the auditory system. This leads to a prediction of the involvement of a novel class of nuclear genes in hearing impairment, namely those with roles in 'mitochondrial protein quality control'.
听力障碍是一种常见疾病，很大程度上起源于遗传，并表现出异质性遗传疾病的典型特征。多达100个独立起作用的核基因与该疾病有关，其中约30个已被定位，但仅确定了少数几个。线粒体DNA突变在综合征性和非综合征性感音神经性听力障碍中也起重要作用。氨基糖苷类抗生素等环境因素以及尚未确定的核基因在听觉表型的表达中与线粒体突变相互作用。与听力障碍相关的不同线粒体突变谱，结合分子水平的机制研究，表明致病过程涉及线粒体内部异常翻译产物在听觉系统敏感细胞中的积累。这导致预测一类新的核基因参与听力障碍，即那些在“线粒体蛋白质质量控制”中起作用的基因。
