Lertrit P, Noer A S, Byrne E, Marzuki S
Department of Biochemistry, Monash University, Clayton, Victoria, Australia.
Hum Genet. 1992 Nov;90(3):251-4. doi: 10.1007/BF00220072.
The distribution of the causal 8344A-->G mtDNA mutation has been examined in six tissues of a patient with myoclonic epilepsy with ragged red fibers (MERRF), to study the developmental genetics of this type of mitochondrial disorder, and to determine the pathophysiological importance of the mtDNA heteroplasmy generally observed in such patients. Heteroplasmy of the mtDNA was observed in all six tissues (cerebellum, cerebrum, pancreas, liver, muscle, and heart) suggesting that, whereas the mtDNA mutation is relatively new, the mutated population must have existed before the formation of the three primary embryonic layers. The tissue distribution reveals significant variations in the ratio between the mutated and the normal mtDNA species, indicating the randomness of mtDNA segregation during developmental cell division and differentiation events. The result suggests the existence of tissue-specific nuclear factor(s) that determines the expression of the 8344A-->G mutation in various tissues; in MERRF syndrome, expression is mainly in the central nervous system.
对一名患有肌阵挛性癫痫伴破碎红纤维（MERRF）的患者的六种组织进行了因果性8344A→G线粒体DNA（mtDNA）突变分布的研究，以探讨这类线粒体疾病的发育遗传学，并确定在此类患者中普遍观察到的mtDNA异质性的病理生理重要性。在所有六种组织（小脑、大脑、胰腺、肝脏、肌肉和心脏）中均观察到mtDNA的异质性，这表明，尽管mtDNA突变相对较新，但突变群体肯定在三个主要胚胎层形成之前就已存在。组织分布显示突变型和正常型mtDNA种类之间的比例存在显著差异，表明在发育性细胞分裂和分化过程中mtDNA分离的随机性。结果提示存在组织特异性核因子，其决定了8344A→G突变在各种组织中的表达；在MERRF综合征中，表达主要在中枢神经系统。
