Kim Han-Joon, Jeon Beom S
Department of Neurology and Movement Disorder Center, Parkinson Study Group, and Neuroscience Research Institute, College of Medicine, Seoul National University, Seoul, Korea.
Exp Neurobiol. 2014 Dec;23(4):271-6. doi: 10.5607/en.2014.23.4.271. Epub 2014 Dec 12.
Mutations causing genetic disorders can occur during mitotic cell division after fertilization, which is called somatic mutations. This leads to somatic mosaicism, where two or more genetically distinct cells are present in one individual. Somatic mutations are the most well studied in cancer where it plays an important role and also have been associated with some neurodegenerative disorders. The study of somatic mosaicism in Parkinson disease (PD) is only in its infancy, and a case with somatic mutation has not yet been described. However, we can speculate that a somatic mutation affecting cells in the central nervous system including substantia nigra dopaminergic neurons could lead to the development of PD through the same pathomechanisms of genetic PD even in the absence of a germ-line mutation. Theoretically, a number of genes could be candidates for genetic analysis for the presence of somatic mosaicism. Among them, SNCA and PARK2 could be the best candidates to analyze. Because analyzing brain tissues in living patients is impossible, alternative tissues could be used to indicate the genetic status of the brain. Performance of the technology is another factor to consider when analyzing the tissues.
导致遗传疾病的突变可在受精后的有丝分裂过程中发生，这被称为体细胞突变。这会导致体细胞嵌合体，即一个个体中存在两种或更多种基因不同的细胞。体细胞突变在癌症中研究得最为充分，它在癌症中起着重要作用，并且也与一些神经退行性疾病有关。帕金森病（PD）中体细胞嵌合体的研究尚处于起步阶段，尚未有体细胞突变病例的描述。然而，我们可以推测，即使在没有种系突变的情况下，影响包括黑质多巴胺能神经元在内的中枢神经系统细胞的体细胞突变也可能通过与遗传性PD相同的发病机制导致PD的发生。理论上，许多基因可能是用于分析体细胞嵌合体存在情况的遗传分析候选基因。其中，α-突触核蛋白（SNCA）和帕金森病2型基因（PARK2）可能是最佳分析候选基因。由于无法对活体患者的脑组织进行分析，可使用替代组织来指示大脑的遗传状态。在分析组织时，技术的性能是另一个需要考虑的因素。
