Alteration in the copy number of mitochondrial DNA in leukocytes of patients with mitochondrial encephalomyopathies
Alteration in the copy number of mitochondrial DNA in leukocytes of patients with mitochondrial encephalomyopathies
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DOI：
10.1111/j.1600-0404.2006.00586.x
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发表时间：
2006-05-01
影响因子：
3.5
通讯作者：
Wei, YH
中科院分区：
文献类型：
--
作者：
Liu, CS;Cheng, WL;Wei, YH
目的 - 我们研究了线粒体 DNA (mtDNA) 突变是否影响线粒体肌病脑病伴乳酸酸中毒和中风样发作 (MELAS) 以及肌阵挛性癫痫伴锯齿状红纤维 (MERRF) 综合征患者的线粒体基因组拷贝数。材料和方法 - 本研究招募了 48 名台湾 MELAS 综合征患者和 20 名 MERRF 综合征患者。结果 - 与对照组相比，MELAS 或 MERRF 综合征患者白细胞中的 mtDNA 拷贝数在年轻时显着较高，但在老年时较低。此外，具有 A3243G 转变的 mtDNA 比例较高的 MELAS 患者的 mtDNA 拷贝数较低。患有多系统疾病的 MELAS 或 MERRF 患者白细胞中 mtDNA 拷贝数较低。此外，在多系统受累的 MERRF 患者的白细胞中发现了更高比例的 4977 bp 缺失的 mtDNA。结论 - 在白细胞中，mtDNA拷贝数的改变与点突变或大规模缺失的mtDNA比例相关，这可能作为MELAS和MERRF综合征发病机制和疾病进展的生物标志物。
Objectives - We investigated whether mutation of mitochondrial DNA (mtDNA) affects the copy number of the mitochondrial genome in patients with mitochondrial myopathy encephalopathy with lactic acidosis and stroke-like episodes (MELAS) and those with myoclonic epilepsy with ragged-red fiber (MERRF) syndromes. Materials and methods - Forty-eight Taiwanese patients with MELAS syndrome and 20 patients with MERRF syndrome were recruited in this study. Results - In relation to controls, the copy numbers of mtDNA in leukocytes of patients with MELAS or MERRF syndrome were significantly higher at a young age but lower at an advanced age. In addition, MELAS patients harboring higher proportions of mtDNA with A3243G transition had lower mtDNA copy numbers. The MELAS or MERRF patients with multi-system disorders had lower mtDNA copy numbers in leukocytes. Furthermore, higher proportions of mtDNA with 4977 bp deletion were found in leukocytes of MERRF patients with multi-system involvement. Conclusion - In leukocytes, alteration in the copy number of mtDNA is related to the proportion of mtDNA with a point mutation or large-scale deletion, which may serve as a biomarker in the pathogenesis and disease progression of MELAS and MERRF syndromes.