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两种影响细胞器数量和蛋白质合成的新型致病性线粒体DNA突变。亮氨酸（UUR）转运RNA基因是一个病因热点吗？

Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis. Is the tRNA(Leu(UUR)) gene an etiologic hot spot?

作者信息

Moraes C T, Ciacci F, Bonilla E, Jansen C, Hirano M, Rao N, Lovelace R E, Rowland L P, Schon E A, DiMauro S

机构信息

Department of Genetics & Development, College of Physicians & Surgeons, Columbia University, New York 10032.

出版信息

J Clin Invest. 1993 Dec;92(6):2906-15. doi: 10.1172/JCI116913.

DOI:10.1172/JCI116913
PMID:8254046
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC288494/
Abstract

We identified two patients with pathogenic single nucleotide changes in two different mitochondrial tRNA genes: the first mutation in the tRNA(Asn) gene, and the ninth known mutation in the tRNA(Leu(UUR)) gene. The mutation in tRNA(Asn) was associated with isolated ophthalmoplegia, whereas the mutation in tRNA(Leu(UUR)) caused a neurological syndrome resembling MERRF (myoclonus epilepsy and ragged-red fibers) plus optic neuropathy, retinopathy, and diabetes. Both mutations were heteroplasmic, with higher percentages of mutant mtDNA in affected tissues, and undetectable levels in maternal relatives. Analysis of single muscle fibers indicated that morphological and biochemical alterations appeared only when the proportions of mutant mtDNA exceeded 90% of the total cellular mtDNA pool. The high incidence of mutations in the tRNA(Leu(UUR)) gene suggests that this region is an "etiologic hot spot" in mitochondrial disease.

摘要

我们鉴定出两名患者，其两个不同的线粒体tRNA基因存在致病性单核苷酸变化：第一个突变位于tRNA(Asn)基因，第二个突变是tRNA(Leu(UUR))基因的第九个已知突变。tRNA(Asn)中的突变与孤立性眼肌麻痹相关，而tRNA(Leu(UUR))中的突变导致一种类似于肌阵挛性癫痫伴破碎红纤维（MERRF）的神经综合征，伴有视神经病变、视网膜病变和糖尿病。两种突变均为异质性，在受影响组织中突变型mtDNA的百分比更高，而在母系亲属中检测不到。对单个肌纤维的分析表明，只有当突变型mtDNA的比例超过细胞总mtDNA库的90%时，才会出现形态学和生化改变。tRNA(Leu(UUR))基因的高突变率表明该区域是线粒体疾病的一个“病因热点”。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ee/288494/68c0c055d750/jcinvest00044-0357-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ee/288494/3a2f97c2f40e/jcinvest00044-0357-b.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ee/288494/8c4eea227a52/jcinvest00044-0358-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ee/288494/97a0d31ba783/jcinvest00044-0359-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ee/288494/f2bef928f115/jcinvest00044-0359-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ee/288494/05fee8ae4384/jcinvest00044-0360-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75ee/288494/c24ff56fff60/jcinvest00044-0360-b.jpg
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