Mosaicism in Tumor Suppressor Gene Syndromes: Prevalence, Diagnostic Strategies, and Transmission Risk.

IF 7.7 2区生物学 Q1 GENETICS & HEREDITY

Annual review of genomics and human genetics Pub Date : 2022-08-31 DOI:10.1146/annurev-genom-120121-105450

Jillian L Chen, David T Miller, Laura S Schmidt, David Malkin, Bruce R Korf, Charis Eng, David J Kwiatkowski, Krinio Giannikou

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引用次数: 5

Abstract

A mosaic state arises when pathogenic variants are acquired in certain cell lineages during postzygotic development, and mosaic individuals may present with a generalized or localized phenotype. Here, we review the current state of knowledge regarding mosaicism for eight common tumor suppressor genes-NF1, NF2, TSC1, TSC2, PTEN, VHL, RB1, and TP53-and their related genetic syndromes/entities. We compare and discuss approaches for comprehensive diagnostic genetic testing, the spectrum of variant allele frequency, and disease severity. We also review affected individuals who have no mutation identified after conventional genetic analysis, as well as genotype-phenotype correlations and transmission risk for each tumor suppressor gene in full heterozygous and mosaic patients. This review provides new insight into similarities as well as marked differences regarding the appreciation of mosaicism in these tumor suppressor syndromes.

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肿瘤抑制基因综合征中的镶嵌现象:患病率、诊断策略和传播风险。

当某些细胞系在受精卵后发育过程中获得致病变异时，就会出现嵌合状态，嵌合个体可能表现为普遍或局部表型。在这里，我们回顾了八种常见肿瘤抑制基因nf1、NF2、TSC1、TSC2、PTEN、VHL、RB1和tp53及其相关遗传综合征/实体的嵌合现象的现状。我们比较和讨论综合诊断基因检测、变异等位基因频率谱和疾病严重程度的方法。我们还回顾了在常规遗传分析后未发现突变的受影响个体，以及在全杂合和马赛克患者中每种肿瘤抑制基因的基因型-表型相关性和传播风险。这篇综述为这些肿瘤抑制综合征中嵌合现象的相似之处和显著差异提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annual review of genomics and human genetics 生物-遗传学

CiteScore

14.90

自引率

1.10%

发文量

期刊介绍： Since its inception in 2000, the Annual Review of Genomics and Human Genetics has been dedicated to showcasing significant developments in genomics as they pertain to human genetics and the human genome. The journal emphasizes genomic technology, genome structure and function, genetic modification, human variation and population genetics, human evolution, and various aspects of human genetic diseases, including individualized medicine.