Institute of Human Genetics. University Hospital Heidelberg, Heidelberg; Institute of Human Genetics, University of Greifswald and Interfaculty Institute for Genetics and Functional Genomics, Greifswald University, Greifswald; Department of Dermatology and Venereology, University Medical Center Freiburg, Albert-Ludwigs-Universität Freiburg, Freiburg; genetikum®, Genetische Beratung und Diagnostik, Stuttgart.
Dtsch Arztebl Int. 2020 Feb 21;116(8):119-125. doi: 10.3238/arztebl.2020.0119.
Genetic mosaics arise through new mutations occurring after fertiliza- tion (i.e., postzygotic mutations). Mosaics have been described in recent years as the cause of many different disorders; many of these are neurocutaneous diseases and syndromal developmental disorders, each with a characteristic phenotype. In some of these disorders, there is a genetic predisposition to the development of tumors. This article is intended as an overview of selected mosaic diseases.
This review is based on publications retrieved by a selective search in PubMed, with particular attention to recent articles in high-ranking journals dealing with asymmetric growth disturbances, focal brain malformations, mosaic diseases due to dysregulation of the RAS/RAF signaling pathway (mosaic RASopathies), and vascular malformations.
The identification of postzygotic mutations has led to the reclassification of traditional disease entities and to a better understanding of their pathogenesis. Diagnosis is aided by modern next-generation sequencing (NGS) techniques that allow the detection even of low-grade mosaics. Many mosaic mutations are not detectable in blood, but only in the affected tissue, e.g., the skin. Genetic mosaic diseases often manifest themselves in the skin and brain, and by facial dysmorphism, asymmetrical growth disturbances, and vascular malformations.
The possibility of a mosaic disease should be kept in mind in the diag- nostic evaluation of patients with asymmetrical growth disturbances, focal neuronal migration disturbances, vascular malformations, and linear skin abnormalities. The demonstration of a postzygotic mutation often affords relief to the parents of an affected child, since this means that there is no increased risk for recurrence of the same disorder in future children. Correct classification is important, as molecular available for certain mosaic diseases, e.g., PIK3CA-related overgrowth spectrum (PROS) disorder.
遗传嵌合体是通过受精后（即合子后突变）发生的新突变而产生的。近年来，嵌合体被描述为许多不同疾病的原因；其中许多是神经皮肤疾病和综合征性发育障碍，每种疾病都有其特征性表型。在这些疾病中，有些存在肿瘤发生的遗传倾向。本文旨在对选定的嵌合疾病进行综述。
本综述基于在 PubMed 中进行选择性搜索获得的出版物，特别关注涉及不对称生长障碍、局灶性脑畸形、由于 RAS/RAF 信号通路失调引起的嵌合疾病（嵌合 RAS 病）和血管畸形的高排名期刊中最近的文章。
合子后突变的鉴定导致了传统疾病实体的重新分类，并更好地了解了它们的发病机制。现代下一代测序（NGS）技术有助于诊断，即使是低级别嵌合体也能被检测到。许多嵌合突变在血液中无法检测到，但仅在受影响的组织中，例如皮肤。遗传嵌合疾病通常在皮肤和大脑中表现出来，并通过面部发育不良、不对称生长障碍和血管畸形表现出来。
在诊断具有不对称生长障碍、局灶性神经元迁移障碍、血管畸形和线性皮肤异常的患者时，应考虑存在嵌合疾病的可能性。如果能检测到合子后突变，通常可以减轻受影响孩子的父母的负担，因为这意味着在未来的孩子中，同一疾病再次发生的风险不会增加。正确的分类很重要，因为某些嵌合疾病（例如，PIK3CA 相关过度生长谱（PROS）障碍）有分子靶向治疗。
