Germinal and Somatic Trisomy 21 Mosaicism: How Common is it, What are the Implications for Individual Carriers and How Does it Come About?
Germinal and Somatic Trisomy 21 Mosaicism: How Common is it, What are the Implications for Individual Carriers and How Does it Come About?
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DOI：
10.2174/138920210793176056
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发表时间：
2010-09
期刊：
影响因子：
2.6
通讯作者：
Iwarsson E
中科院分区：
文献类型：
--
作者：
Hultén MA;Jonasson J;Nordgren A;Iwarsson E
众所周知，在人类群体中可能存在不同程度的21三体嵌合体，主要是个体组织中正常细胞和21三体细胞的组合。这涉及发生在生殖细胞系中的21三体嵌合体和记录在不同体细胞组织中的21三体嵌合体，或者实际上在相同受试者中两者的组合。然而，关于21三体嵌合体在具有唐氏综合征临床特征的人以及普通人群的不同组织样本中的发生率的信息仍然有限。这种缺乏详细知识的主要原因之一是其鉴定的技术问题，其中特别是低级/隐蔽的21三体嵌合现象，即在少于3-5%的相应组织中发生的嵌合现象，只能通过荧光原位杂交（FISH）方法在来自不同组织样品的大细胞群上确定。在这篇综述中，我们总结了目前在这一领域的知识，特别是关于在一般人群中可能发生的衰老和体细胞21三体嵌合体及其起源机制的问题。我们还强调了这种类型的非整倍体嵌合体个体运营商的生殖和临床意义。我们的结论是，生育21三体唐氏综合征患儿的风险很可能与任何携带者父母生殖系中21三体细胞的发生率有关。个体携带者的临床意义可能同样取决于相关体细胞组织中21三体的发生率。值得注意的是，例如，有迹象表明21三体嵌合体将使携带者易患儿童白血病和阿尔茨海默病等疾病，但另一方面，实体癌的风险可能会大大降低。
It is well known that varying degrees of mosaicism for Trisomy 21, primarily a combination of normal and Trisomy 21 cells within individual tissues, may exist in the human population. This involves both Trisomy 21 mosaicism occurring in the germ line and Trisomy 21 mosaicism documented in different somatic tissues, or indeed a combination of both in the same subjects. Information on the incidence of Trisomy 21 mosaicism in different tissue samples from people with clinical features of Down syndrome as well as in the general population is, however, still limited. One of the main reasons for this lack of detailed knowledge is the technological problem of its identification, where in particular low grade/cryptic Trisomy 21 mosaicism, i.e. occurring in less than 3-5% of the respective tissues, can only be ascertained by fluorescence in situ hybridization (FISH) methods on large cell populations from the different tissue samples. In this review we summarize current knowledge in this field with special reference to the question on the likely incidence of germinal and somatic Trisomy 21 mosaicism in the general population and its mechanisms of origin. We also highlight the reproductive and clinical implications of this type of aneuploidy mosaicism for individual carriers. We conclude that the risk of begetting a child with Trisomy 21 Down syndrome most likely is related to the incidence of Trisomy 21 cells in the germ line of any carrier parent. The clinical implications for individual carriers may likewise be dependent on the incidence of Trisomy 21 in the relevant somatic tissues. Remarkably, for example, there are indications that Trisomy 21 mosaicism will predispose carriers to conditions such as childhood leukemia and Alzheimer’s Disease but there is on the other hand a possibility that the risk of solid cancers may be substantially reduced.