Department of Genetic Medicine and Development, University of Geneva Medical School and University Hospitals of Geneva, 1 rue Michel-Servet, 1211 Geneva, Switzerland.
Nat Rev Genet. 2017 Mar;18(3):147-163. doi: 10.1038/nrg.2016.154. Epub 2016 Dec 28.
Down syndrome (also known as trisomy 21) is the model human phenotype for all genomic gain dosage imbalances, including microduplications. The functional genomic exploration of the post-sequencing years of chromosome 21, and the generation of numerous cellular and mouse models, have provided an unprecedented opportunity to decipher the molecular consequences of genome dosage imbalance. Studies of Down syndrome could provide knowledge far beyond the well-known characteristics of intellectual disability and dysmorphic features, as several other important features, including congenital heart defects, early ageing, Alzheimer disease and childhood leukaemia, are also part of the Down syndrome phenotypic spectrum. The elucidation of the molecular mechanisms that cause or modify the risk for different Down syndrome phenotypes could lead to the introduction of previously unimaginable therapeutic options.
唐氏综合征（也称为 21 三体综合征）是所有基因组增益剂量失衡（包括微重复）的人类表型模型。在 21 号染色体测序后的几年中，对其进行功能基因组的探索，并生成了大量的细胞和小鼠模型，为破译基因组剂量失衡的分子后果提供了前所未有的机会。唐氏综合征的研究不仅可以提供超出智力障碍和畸形特征等已知特征的知识，还可以了解其他一些重要特征，包括先天性心脏病、早老症、阿尔茨海默病和儿童白血病，这些特征也是唐氏综合征表型谱的一部分。阐明导致或改变不同唐氏综合征表型风险的分子机制，可以带来以前难以想象的治疗选择。
