Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH University Aachen, Pauwelsstr. 3, D-52074 Aachen, Germany.
Genes (Basel). 2024 Jan 26;15(2):163. doi: 10.3390/genes15020163.
Genomic imprinting is a specific mode of gene regulation which particularly accounts for the factors involved in development. Its disturbance affects the fetus, the course of pregnancy and even the health of the mother. In children, aberrant imprinting signatures are associated with imprinting disorders (ImpDis). These alterations also affect the function of the placenta, which has consequences for the course of the pregnancy. The molecular causes of ImpDis comprise changes at the DNA level and methylation disturbances (imprinting defects/ImpDefs), and there is an increasing number of reports of both pathogenic fetal and maternal DNA variants causing ImpDefs. These ImpDefs can be inherited, but prediction of the pregnancy complications caused is difficult, as they can cause miscarriages, aneuploidies, health issues for the mother and ImpDis in the child. Due to the complexity of imprinting regulation, each pregnancy or patient with suspected altered genomic imprinting requires a specific workup to identify the precise molecular cause and also careful clinical documentation. This review will cover the current knowledge on the molecular causes of aberrant imprinting signatures and illustrate the need to identify this basis as the prerequisite for personalized genetic and reproductive counselling of families.
基因组印记是一种特定的基因调控模式，特别涉及到发育过程中的因素。其紊乱会影响胎儿、妊娠过程甚至母亲的健康。在儿童中，异常的印记特征与印记疾病（ImpDis）有关。这些改变还会影响胎盘的功能，从而对妊娠过程产生影响。ImpDis 的分子病因包括 DNA 水平的变化和甲基化紊乱（印记缺陷/ImpDefs），越来越多的报道表明胎儿和母体的致病性 DNA 变异会导致 ImpDefs。这些 ImpDefs 可以遗传，但由于它们会导致流产、非整倍体、母亲的健康问题和儿童的 ImpDis，因此很难预测导致的妊娠并发症。由于印记调控的复杂性，每一次妊娠或疑似异常基因组印记的患者都需要进行特定的检查，以确定确切的分子病因，并进行仔细的临床记录。这篇综述将涵盖异常印记特征的分子病因的最新知识，并说明有必要确定这一基础，作为对有印记疾病家族进行个性化遗传和生殖咨询的前提。
