CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA IS ASSOCIATED WITH A NOVEL MUTATION IN THE MITOCHONDRIAL TRNA(ASN) GENE
CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA IS ASSOCIATED WITH A NOVEL MUTATION IN THE MITOCHONDRIAL TRNA(ASN) GENE
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DOI：
10.1006/bbrc.1994.2485
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发表时间：
1994-10-28
影响因子：
3.1
通讯作者：
REICHMANN, H
中科院分区：
文献类型：
--
作者：
SEIBEL, P;LAUBER, J;REICHMANN, H
慢性进行性眼外肌麻痹（CPEO）是由50%的患者中由于线粒体基因组的大规模缺失而导致的氧化磷酸化（OXPHOS）活性降低引起的。缺失包括结构OXPHOS基因以及其表达所需的tRNA基因，使得发病机制可能是由于缺失的OXPHOS亚基或受损的线粒体翻译。我们已经分析了一个病人的线粒体基因组呈现与CPEO单碱基取代，并发现了一个新的异质性突变的tRNA（Asn）基因的位置5692转换成鸟嘌呤的高度保守的腺嘌呤。这种突变是独特的，因为它位于反密码子环到反密码子茎的过渡处，并导致额外的碱基对，从而将形成环的核苷酸数量从7个减少到5个。我们的研究结果表明，CPEO可能是由线粒体tRNA基因中的单个碱基取代引起的，因此线粒体蛋白质合成成为OXPHOS保真度的限速步骤。(C)1994年出版社出版。
Chronic progressive external ophthalmoplegia (CPEO) is caused by a decreased oxidative phosphorylation (OXPHOS) activity due to large-scale deletions of the mitochondrial genome in 50 % of the patients. The deletions encompass structural OXPHOS genes as well as tRNA genes, required for their expression so that the pathogenesis could be due to the deleted OXPHOS subunits or to an impaired mitochondrial translation. We have analyzed the mitochondrial genome of a patient presenting with CPEO for single base substitutions and discovered a novel heteroplasmic mutation in the tRNA(Asn) gene at position 5692 that converts a highly conserved adenine into a guanine. This mutation is unique because it is located at the transition of the anticodon loop to the anticodon stem and it leads to an additional base pair, thus reducing the number of loop-forming nucleotides from seven to five. Our findings suggest that CPEO can be caused by a single base substition in a mitochondrial tRNA gene so that the mitochondrial protein synthesis becomes the rate limiting step in OXPHOS fidelity. (C) 1994 Academic Press, Inc.