Parenti Ilaria, Kaiser Frank J
Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
Essener Zentrum für Seltene Erkrankungen (EZSE), Universitätsklinikum Essen, Essen, Germany.
Front Neurosci. 2021 Nov 5;15:774950. doi: 10.3389/fnins.2021.774950. eCollection 2021.
Chromatinopathies can be defined as a class of neurodevelopmental disorders caused by mutations affecting proteins responsible for chromatin remodeling and transcriptional regulation. The resulting dysregulation of gene expression favors the onset of a series of clinical features such as developmental delay, intellectual disability, facial dysmorphism, and behavioral disturbances. Cornelia de Lange syndrome (CdLS) is a prime example of a chromatinopathy. It is caused by mutations affecting subunits or regulators of the cohesin complex, a multisubunit protein complex involved in various molecular mechanisms such as sister chromatid cohesion, transcriptional regulation and formation of topologically associated domains. However, disease-causing variants in non-cohesin genes with overlapping functions have also been described in association with CdLS. Notably, the majority of these genes had been previously found responsible for distinct neurodevelopmental disorders that also fall within the category of chromatinopathies and are frequently considered as differential diagnosis for CdLS. In this review, we provide a systematic overview of the current literature to summarize all mutations in non-cohesin genes identified in association with CdLS phenotypes and discuss about the interconnection of proteins belonging to the chromatinopathies network.
染色质病可定义为一类由影响负责染色质重塑和转录调控的蛋白质的突变引起的神经发育障碍。由此导致的基因表达失调有利于一系列临床特征的出现，如发育迟缓、智力残疾、面部畸形和行为障碍。科妮莉亚·德·朗格综合征（CdLS）是染色质病的一个典型例子。它是由影响黏连蛋白复合体亚基或调节因子的突变引起的，黏连蛋白复合体是一种多亚基蛋白质复合体，参与各种分子机制，如姐妹染色单体黏连、转录调控和拓扑相关结构域的形成。然而，也有报道称，具有重叠功能的非黏连蛋白基因中的致病变异与CdLS有关。值得注意的是，这些基因中的大多数此前已被发现与不同的神经发育障碍有关，这些障碍也属于染色质病范畴，并且经常被视为CdLS的鉴别诊断。在这篇综述中，我们对当前文献进行了系统概述，以总结与CdLS表型相关的非黏连蛋白基因中鉴定出的所有突变，并讨论属于染色质病网络的蛋白质之间的相互联系。
