Mutations occurring during embryonic development affect only a subset of cells resulting in two or more distinct cell populations that are present at different levels, also known as postzygotic mosaicism (PZM). Although PZM is a common biological phenomenon, it is often overlooked as a source of disease due to the challenges associated with its detection and characterization, especially for very low‐frequency variants. Moreover, PZM can cause a different phenotype compared to constitutional mutations. Especially, lethal mutations in receptor tyrosine kinase (RTK) pathway genes, which exist only in a mosaic state, can have completely new clinical manifestations and can look very different from the associated monogenic disorder. However, some key questions are still not addressed, such as the level of mosaicism resulting in a pathogenic phenotype and how the clinical outcome changes with the development and age. Addressing these questions is not trivial as we require methods with the sensitivity to capture some of these variants hidden away in very few cells. Recent ultra‐accurate deep‐sequencing approaches can now identify these low‐level mosaics and will be central to understand systemic and local effects of mosaicism in the RTK pathway. The main focus of this review is to highlight the importance of low‐level mosaics and the need to include their detection in studies of genomic variation associated with disease.

中文翻译：

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酪氨酸受体激酶途径中的致病性合子后镶嵌：潜在的未知人类疾病隐藏在少数细胞中

在胚胎发育过程中发生的突变仅影响细胞的一个子集，导致以不同水平存在的两个或多个不同的细胞群，也称为后合子镶嵌（PZM）。尽管PZM是一种常见的生物学现象，但是由于其检测和表征（特别是对于非常低频的变体）带来的挑战，它经常被忽略为疾病的来源。而且，与结构突变相比，PZM可以引起不同的表型。尤其是，仅以镶嵌状态存在的受体酪氨酸激酶（RTK）途径基因中的致死突变可以具有全新的临床表现，并且看起来与相关的单基因疾病非常不同。但是，一些关键问题仍未解决，例如导致病原体表型的镶嵌水平，以及临床结果如何随着年龄和年龄的变化而变化。解决这些问题并非易事，因为我们需要能够敏感地捕获隐藏在极少数单元格中的某些变体的方法。现在，最近的超高精度深度测序方法可以识别这些低水平的镶嵌图，对于了解RTK途径中镶嵌现象的系统性和局部性影响至关重要。这篇综述的主要重点是强调低水平镶嵌的重要性以及在与疾病相关的基因组变异研究中包括其检测的必要性。现在，最近的超高精度深度测序方法可以识别这些低水平的镶嵌图，对于了解RTK途径中镶嵌现象的系统性和局部性影响至关重要。这篇综述的主要重点是强调低水平镶嵌的重要性以及在与疾病相关的基因组变异研究中包括其检测的必要性。现在，最近的超高精度深度测序方法可以识别这些低水平的镶嵌图，对于了解RTK途径中镶嵌现象的系统性和局部性影响至关重要。这篇综述的主要重点是强调低水平镶嵌的重要性以及在与疾病相关的基因组变异研究中包括其检测的必要性。