Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
Front Immunol. 2021 Nov 16;12:783022. doi: 10.3389/fimmu.2021.783022. eCollection 2021.
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.
倒位镶嵌现象在越来越多的遗传疾病中被报道，包括原发性免疫缺陷疾病。有几种机制可以介导遗传突变的体体细胞倒位。回复突变恢复野生型序列，而第二点突变导致补偿性变化。此外，在镶嵌个体中已经证明存在基因内重组、染色体缺失和非等位基因杂合性丢失。在一些具有回复镶嵌现象的免疫缺陷患者中，恢复野生型功能的回复细胞可能与更轻微的疾病表型相关。回复细胞也可能导致免疫失调。在同一个体中鉴定出大量不同遗传变化的研究进一步支持原发性免疫缺陷疾病中回复镶嵌现象的频繁发生。这种现象还为评估不同细胞谱系中恢复基因表达的生物学效应提供了独特的机会。本文综述了原发性免疫缺陷疾病中回复镶嵌现象的最新发现，并讨论了其临床意义。
