Down syndrome.
Down syndrome.
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DOI：
10.1038/s41572-019-0143-7
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发表时间：
2020-02-06
期刊：
影响因子：
--
通讯作者：
Reeves RH
中科院分区：
文献类型：
--
作者：
Antonarakis SE;Skotko BG;Rafii MS;Strydom A;Pape SE;Bianchi DW;Sherman SL;Reeves RH
21三体，即多余的21号染色体的存在，导致一系列通常被称为唐氏综合征（DS）的临床特征。退行性椎体滑移是一种遗传上最复杂的与人类产后生存相容的疾病，也是最常见的可存活的常染色体非整倍体。涉及人类21号染色体全部或部分三体或同源小鼠基因组区域的小鼠退行性变性模型，为了解三复制基因或基因群对退行性变性许多临床表现的贡献提供了有价值的见解。这一努力是具有挑战性的，因为21号染色体上有大约200个蛋白质编码基因，它们可以直接或间接地影响细胞、组织、器官和系统的稳态。尽管这种复杂性对理解退行性椎体滑移的许多临床特征的潜在分子基础构成了巨大的挑战，但它也为提高对许多细胞类型、组织、器官和系统发育和功能的遗传机制的理解提供了机会。自从第一次描述21三体以来，我们对先天性心脏病的智力残疾和遗传风险因素有了更多的了解。在患有退行性变性的个体中，实体瘤的发生率较低，这支持了21号染色体基因的鉴定，这些基因在过度表达时可以防止癌症。阿尔茨海默病组织病理学的普遍发生和退行性痴呆的高患病率为阿尔茨海默病的病理和治疗提供了新的见解。改善退行性痴呆患者智力残疾的临床试验标志着一个新时代的到来，在这个时代中，基于退行性痴呆分子病理生理学知识的治疗干预可以被探索；这些努力为未来提供了合理的希望。
Trisomy 21, the presence of a supernumerary chromosome 21, results in a collection of clinical features commonly known as Down syndrome (DS). DS is among the most genetically complex of the conditions that are compatible with human survival post-term, and the most frequent survivable autosomal aneuploidy. Mouse models of DS, involving trisomy of all or part of human chromosome 21 or orthologous mouse genomic regions, are providing valuable insights into the contribution of triplicated genes or groups of genes to the many clinical manifestations in DS. This endeavour is challenging, as there are >200 protein-coding genes on chromosome 21 and they can have direct and indirect effects on homeostasis in cells, tissues, organs and systems. Although this complexity poses formidable challenges to understanding the underlying molecular basis for each of the many clinical features of DS, it also provides opportunities for improving understanding of genetic mechanisms underlying the development and function of many cell types, tissues, organs and systems. Since the first description of trisomy 21, we have learned much about intellectual disability and genetic risk factors for congenital heart disease. The lower occurrence of solid tumours in individuals with DS supports the identification of chromosome 21 genes that protect against cancer when overexpressed. The universal occurrence of the histopathology of Alzheimer disease and the high prevalence of dementia in DS are providing insights into the pathology and treatment of Alzheimer disease. Clinical trials to ameliorate intellectual disability in DS signal a new era in which therapeutic interventions based on knowledge of the molecular pathophysiology of DS can now be explored; these efforts provide reasonable hope for the future.
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影响因子：
4.2
作者：
Annus T;Wilson LR;Acosta-Cabronero J;Cardenas-Blanco A;Hong YT;Fryer TD;Coles JP;Menon DK;Zaman SH;Holland AJ;Nestor PJ
通讯作者：
Nestor PJ
影响因子：
5.3
作者：
Allen EG;Freeman SB;Druschel C;Hobbs CA;O'Leary LA;Romitti PA;Royle MH;Torfs CP;Sherman SL
通讯作者：
Sherman SL
影响因子：
30.8
作者：
ANTONARAKIS, SE;AVRAMOPOULOS, D;SCHINZEL, AA
通讯作者：
SCHINZEL, AA
DOI：
10.1016/j.ijporl.2013.05.027
发表时间：
2013-08-01
影响因子：
1.5
作者：
Austeng, Marit Erna;Akre, Harriet;Kvaerner, Kari Jorunn
通讯作者：
Kvaerner, Kari Jorunn
影响因子：
3
作者：
Becker, Walter;Soppa, Ulf;Tejedor, Francisco J.
通讯作者：
Tejedor, Francisco J.