Reversion Mosaicism in Primary Immunodeficiency Diseases.
Reversion Mosaicism in Primary Immunodeficiency Diseases.
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DOI：
10.3389/fimmu.2021.783022
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发表时间：
2021
影响因子：
7.3
通讯作者：
Wada T
中科院分区：
文献类型：
--
作者：
Miyazawa H;Wada T
在包括原发性免疫缺陷疾病在内的越来越多的遗传疾病中报道了逆转镶嵌现象。有几种机制可以介导遗传突变的体细胞逆转。反向突变恢复野生型序列，而第二位点突变导致代偿性变化。此外，基因内重组、染色体缺失和拷贝中性的杂合性缺失已在马赛克个体中得到证实。在一些具有逆转嵌合体的免疫缺陷患者中，恢复野生型功能的逆转细胞可能与较轻的疾病表型相关。逆转录细胞也可能导致免疫失调。在同一个体中发现多种遗传变化的研究进一步支持了在原发性免疫缺陷疾病中经常发生的逆转镶嵌现象。这一现象也为评估不同细胞系中恢复的基因表达的生物学效应提供了独特的机会。本文综述了近年来在原发性免疫缺陷疾病中发现的逆行嵌合现象，并讨论了其临床意义。
Reversion mosaicism has been reported in an increasing number of genetic disorders including primary immunodeficiency diseases. Several mechanisms can mediate somatic reversion of inherited mutations. Back mutations restore wild-type sequences, whereas second-site mutations result in compensatory changes. In addition, intragenic recombination, chromosomal deletions, and copy-neutral loss of heterozygosity have been demonstrated in mosaic individuals. Revertant cells that have regained wild-type function may be associated with milder disease phenotypes in some immunodeficient patients with reversion mosaicism. Revertant cells can also be responsible for immune dysregulation. Studies identifying a large variety of genetic changes in the same individual further support a frequent occurrence of reversion mosaicism in primary immunodeficiency diseases. This phenomenon also provides unique opportunities to evaluate the biological effects of restored gene expression in different cell lineages. In this paper, we review the recent findings of reversion mosaicism in primary immunodeficiency diseases and discuss its clinical implications.
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影响因子：
82.9
作者：
Gattinoni L;Speiser DE;Lichterfeld M;Bonini C
通讯作者：
Bonini C
影响因子：
3.9
作者：
Du, W;Kumaki, S;Tsuchiya, S
通讯作者：
Tsuchiya, S
影响因子：
4.6
作者：
Bayer, D. K.;Martinez, C. A.;Stray-Pedersen, A.
通讯作者：
Stray-Pedersen, A.
影响因子：
20.3
作者：
Arredondo-Vega, FX;Santisteban, I;Hershfield, MS
通讯作者：
Hershfield, MS
影响因子：
9.1
作者：
Ban, Sol A.;Salzer, Elisabeth;Eibl, Martha M.;Linder, Angela;Geier, Christoph B.;Santos-Valente, Elisangela;Garncarz, Wojciech;Lion, Thomas;Ott, Raphael;Seelbach, Christoph;Boztug, Kaan;Wolf, Hermann M.
通讯作者：
Wolf, Hermann M.