Mitochondrial DNA content is decreased in autosomal dominant optic atrophy
Mitochondrial DNA content is decreased in autosomal dominant optic atrophy
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DOI：
10.1212/01.wnl.0000157282.76715.b1
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发表时间：
2005-03-22
期刊：
影响因子：
9.9
通讯作者：
Park, SS
中科院分区：
文献类型：
--
作者：
Kim, JY;Hwang, JM;Park, SS
背景：常染色体显性遗传性视神经萎缩是遗传性视神经病变中最常见的一种。编码动力蛋白相关线粒体蛋白的OPA1基因突变是ADOA的基础，并可能扰乱线粒体的生物发生和维持。目的：研究OPA1基因突变谱，探讨OPA1基因突变对线粒体含量的影响。方法：对16例临床疑似ADOA的韩国患者进行研究。用聚合酶链式反应-单链构象多态分析和测序分析OPA1基因突变谱，用实时荧光定量聚合酶链式反应检测线粒体DNA含量。结果：共发现8个不同的突变，其中包括5个新突变。实时定量聚合酶链式反应分析显示，线粒体DNA拷贝数的测定具有良好的线性和精密度。OPA1基因突变患者(7~40岁)的每细胞线粒体DNA拷贝数显著低于所有正常对照组(p=0.037)，尤其是10~39岁的正常对照组(p=0.022)。结论：常染色体显性遗传性视神经病变患者的OPA1基因突变谱具有明显的遗传异质性，线粒体DNA含量较低，为OPA1基因突变的致病作用提供了直接证据。
Background: Autosomal dominant optic atrophy ( ADOA) is the commonest form of inherited optic neuropathy. Mutations in the OPA1 gene encoding a dynamin-related mitochondrial protein underlie ADOA and may perturb the biogenesis and maintenance of mitochondria. Objective: To investigate the mutation spectrum of the OPA1 gene and assess alterations in mitochondrial content caused by OPA1 mutations. Methods: Sixteen Korean patients with clinically suspected ADOA were studied. The mutation spectrum of the OPA1 gene was analyzed by PCR single-strand conformation polymorphism and sequencing, and mitochondrial DNA ( mtDNA) content was quantified by real-time PCR. Results: Eight different mutations were found, including five novel mutations. Quantitative real-time PCR analysis showed excellent linearity and precision for the determination of mtDNA copy numbers. The number of mtDNA copies per cell in patients with OPA1 gene mutations ( ages 7 to 40) was significantly lower than those in all normal control subjects ( p = 0.037), particularly lower than in normal control subjects ages 10 to 39 ( p = 0.022). Conclusion: The mutation spectrum of the OPA1 gene disclosed marked genetic heterogeneity and the mitochondrial DNA content was found to be lower in autosomal dominant optic neuropathy, which provides direct evidence for a pathogenetic role of mutations of the OPA1 gene.