Soellner L, Begemann M, Mackay D J G, Grønskov K, Tümer Z, Maher E R, Temple I K, Monk D, Riccio A, Linglart A, Netchine I, Eggermann T
Department of Human Genetics, RWTH Aachen, Aachen, Germany.
Human Genetics and Genomic Medicine, Faculty of Medicine University of Southampton, Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.
Clin Genet. 2017 Jan;91(1):3-13. doi: 10.1111/cge.12827. Epub 2016 Aug 4.
Imprinting disorders (ImpDis) are a group of currently 12 congenital diseases with common underlying (epi)genetic etiologies and overlapping clinical features affecting growth, development and metabolism. In the last years it has emerged that ImpDis are characterized by the same types of mutations and epimutations, i.e. uniparental disomies, copy number variations, epimutations, and point mutations. Each ImpDis is associated with a specific imprinted locus, but the same imprinted region can be involved in different ImpDis. Additionally, even the same aberrant methylation patterns are observed in different phenotypes. As some ImpDis share clinical features, clinical diagnosis is difficult in some cases. The advances in molecular and clinical diagnosis of ImpDis help to circumvent these issues, and they are accompanied by an increasing understanding of the pathomechanism behind them. As these mechanisms have important roles for the etiology of other common conditions, the results in ImpDis research have a wider effect beyond the borders of ImpDis. For patients and their families, the growing knowledge contributes to a more directed genetic counseling of the families and personalized therapeutic approaches.
印记障碍（ImpDis）是一组目前已知的12种先天性疾病，它们具有共同的潜在（表观）遗传病因，且临床特征相互重叠，影响生长、发育和代谢。近年来发现，印记障碍的特征是相同类型的突变和表观突变，即单亲二体、拷贝数变异、表观突变和点突变。每种印记障碍都与一个特定的印记基因座相关，但同一个印记区域可能涉及不同的印记障碍。此外，在不同的表型中甚至也观察到相同的异常甲基化模式。由于一些印记障碍具有共同的临床特征，某些情况下临床诊断较为困难。印记障碍分子和临床诊断方面的进展有助于解决这些问题，同时人们对其背后的发病机制也有了越来越深入的了解。由于这些机制在其他常见疾病的病因中也起着重要作用，印记障碍研究的结果所产生的影响超出了印记障碍的范畴。对于患者及其家庭而言，不断增长的知识有助于为家庭提供更具针对性的遗传咨询和个性化的治疗方法。
