ANALYSIS OF THE TISSUE DISTRIBUTION AND INHERITANCE OF HETEROPLASMIC MITOCHONDRIAL-DNA POINT MUTATION BY DENATURING GRADIENT GEL-ELECTROPHORESIS IN MERRF SYNDROME
ANALYSIS OF THE TISSUE DISTRIBUTION AND INHERITANCE OF HETEROPLASMIC MITOCHONDRIAL-DNA POINT MUTATION BY DENATURING GRADIENT GEL-ELECTROPHORESIS IN MERRF SYNDROME
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DOI：
10.1016/s0960-8966(06)80003-9
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发表时间：
1992-01-01
影响因子：
2.8
通讯作者：
FARDEAU, M
中科院分区：
文献类型：
--
作者：
LOMBES, A;DIAZ, C;FARDEAU, M
肌阵挛性癫痫和破碎红纤维综合征（MERRF）是一种母系遗传性疾病，最近发现线粒体DNA（mtDNA）点突变。突变总是异质性的，即正常和突变的mtDNA在同一个体内共存。我们研究了两个家族的线粒体DNA异质性MERRF综合征，使用变性梯度凝胶电泳技术，避免了错误的限制性内切酶切割的情况下扩增的异质性DNA的野生型/突变型mtDNA的比例的评价。在两名患者中，肌肉突变mtDNA的比例与肌肉线粒体增殖，能量缺乏和I型纤维优势的严重程度一致。在一个家族的三代9例患者中，白细胞中突变mtDNA的比例与疾病的临床严重程度相对一致。突变mtDNA通过这三代的传递没有表现出任何同质性的倾向。在脑、肝、肌肉和心脏中，同一患者的不同组织中突变mtDNA比例的均一性得到证实，但在培养的皮肤成纤维细胞中记录了有丝分裂期间突变mtDNA比例发散的可能性。
MERRF (Myoclonic Epilepsy and Ragged-Red Fibres) syndrome is one of the maternally inherited diseases for which a mitochondrial DNA (mtDNA) point mutation has recently been identified. The mutation is always heteroplasmic, that is normal and mutant mtDNA coexist within the same individual. We studied mtDNA heteroplasmy in two families with MERRF syndrome, using a denaturing gradient gel electrophoresis technique that avoids the errors in the evaluation of wild/mutant mtDNA ratios caused by restriction enzyme cutting in the situation of amplification of a heteroplasmic DNA. In two patients, the proportion of muscle mutant mtDNA was in agreement with the severity of muscle mitochondrial proliferation, energy defect and fibre type I predominance. In nine patients from three generations of one family, mutant mtDNA proportion in leukocytes was in relative agreement with the clinical severity of the disease. Transmission of mutant mtDNA through these three generations did not show any tendency toward homoplasmy. Homogeneity of the mutant mtDNA proportion among different tissues from one patient was demonstrated in brain, liver, muscle and heart but a possibility of divergence of the mutant mtDNA proportion during mitosis was documented in cultured skin fibroblasts.