Safaei Sepideh, Houshmand Massoud, Banoei Mohammad Mehdi, Panahi Mehdi Shafa Shariat, Nafisi Shahriar, Parivar Kazem, Rostami Maryam, Shariati Parvin
Research and Sciences Campus, Azad University, Tehran, Iran.
Neurodegener Dis. 2009;6(1-2):16-22. doi: 10.1159/000170885. Epub 2008 Nov 5.
The spinocerebellar ataxias (SCA) comprise a heterogeneous group of severe late-onset neurodegenerative diseases that are promoted by the expansion of a tandem-arrayed DNA sequence that modifies the primary structure of the protein.
Genomic DNA of 20 patients affected with SCAs was extracted from peripheral blood and screened for deletions in mitochondrial DNA (mtDNA). Sequencing of tRNA(Leu), tRNA(Lys), cytochrome oxidase II, ATPase 6/8 and NADH dehydrogenase I (NDI) genes belonging to mtDNA from patients with SCAs was also carried out to detect the presence of variations.
We identified cytosine-adenine-guanine (CAG) trinucleotide repeat expansions in 20 patients. Seven of these patients had at least one nucleotide change in mtDNA. In such cases, 5 nucleotide variations resulted in amino acid changes with two novel variations T8256G and G9010A.
SCA patients showed high levels of mtDNA variations in lymphocytes. It can be proposed that the SCA gene proteins (Ataxins) are involved in the complicated intracellular mechanisms that affect cellular organelles and their components, such as the mitochondrial genome. The instability of CAG repeats in polyglutamine diseases such as SCAs and Huntington's disease might be a causative factor in mtDNA variation or possible damage.
脊髓小脑共济失调（SCA）是一组异质性严重迟发性神经退行性疾病，由串联排列的DNA序列扩增所致，该扩增会改变蛋白质的一级结构。
从20例SCA患者的外周血中提取基因组DNA，筛查线粒体DNA（mtDNA）的缺失情况。对SCA患者mtDNA中的tRNA（Leu）、tRNA（Lys）、细胞色素氧化酶II、ATP酶6/8和NADH脱氢酶I（NDI）基因进行测序，以检测变异的存在。
我们在20例患者中鉴定出胞嘧啶-腺嘌呤-鸟嘌呤（CAG）三核苷酸重复扩增。其中7例患者的mtDNA至少有一个核苷酸变化。在这些病例中，5个核苷酸变异导致氨基酸变化，有两个新的变异T8256G和G9010A。
SCA患者淋巴细胞中的mtDNA变异水平较高。可以推测，SCA基因蛋白（共济失调蛋白）参与了影响细胞器及其成分（如线粒体基因组）的复杂细胞内机制。在诸如SCA和亨廷顿舞蹈症等多聚谷氨酰胺疾病中，CAG重复序列的不稳定性可能是mtDNA变异或可能损伤的一个致病因素。
