MITOCHONDRIAL RIBOSOMAL-RNA MUTATION ASSOCIATED WITH BOTH ANTIBIOTIC-INDUCED AND NON-SYNDROMIC DEAFNESS
MITOCHONDRIAL RIBOSOMAL-RNA MUTATION ASSOCIATED WITH BOTH ANTIBIOTIC-INDUCED AND NON-SYNDROMIC DEAFNESS
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DOI：
10.1038/ng0793-289
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发表时间：
1993-07-01
期刊：
影响因子：
30.8
通讯作者：
FISCHELGHODSIAN, N
中科院分区：
文献类型：
--
作者：
PREZANT, TR;AGAPIAN, JV;FISCHELGHODSIAN, N
最近在对氨基糖苷类耳毒性敏感的家系和一个大的阿拉伯-以色列家系中描述了母体传播的非综合征性耳聋。由于氨基糖苷类抗生素对细菌核糖体的作用，我们分析了三个不相关的家族性氨基糖苷类抗生素性耳聋患者的线粒体rRNA基因序列。我们还对阿拉伯-以色列血统的完整线粒体基因组进行了测序。所有四个家族在12 S rRNA基因中共享核苷酸1555 A至G取代，该位点与氨基糖苷类活性有关。我们的研究首次描述了导致疾病的线粒体rRNA突变，第一例由线粒体DNA突变引起的非综合征性耳聋，以及第一次对哮喘诱导的耳毒性进行分子遗传学研究。
Maternally transmitted non-syndromic deafness was described recently both in pedigrees with susceptibility to aminoglycoside ototoxicity and in a large Arab-Israeli pedigree. Because of the known action of aminoglycosides on bacterial ribosomes, we analysed the sequence of the mitochondrial rRNA genes of three unrelated patients with familial aminoglycoside-induced deafness. We also sequenced the complete mitochondrial genome of the Arab-Israeli pedigree. All four families shared a nucleotide 1555 A to G substitution in the 12S rRNA gene, a site implicated in aminoglycoside activity. Our study offers the first description of a mitochondrial rRNA mutation leading to disease, the first cases of non-syndromic deafness caused by a mitochondrial DNA mutation and the first molecular genetic study of antibiotic-induced ototoxicity.