Division of Human and Molecular Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Adv Exp Med Biol. 2010;685:111-23.
Cornelia de Lange syndrome (CdLS) (OMIM # 122470, #300590 and #610759) is an autosomal dominant disorder that is classically characterized by typical facial features, growth and mental retardation, upper limb defects, hirsutism, gastrointestinal and other visceral system involvement. Heterozygous mutations in the cohesin regulator, NIPBL, or the cohesin structural components SMC1A and SMC3, have been identified in approximately 65% of individuals with CdLS. Cohesin regulates sister chromatid cohesion during the mitotis and meiosis. In addition, cohesin has been demonstrated to play a critical role in the regulation of gene expression. Furthermore, multiple proteins in the cohesin pathway are also involved in additional fundamental biological events such as double strand DNA break repair, chromatin remodeling and maintaining genomic stability. Here, we will discuss the biology ofcohesin and its associated factors, with emphasis on the clinical manifestations of CdLS and mechanistic studies of the CdLS related proteins.
康尼氏综合征(CdLS)(OMIM #122470、#300590 和#610759)是一种常染色体显性疾病,其特征通常包括典型的面部特征、生长和智力发育迟缓、上肢缺陷、多毛症、胃肠道和其他内脏系统受累。约 65%的 CdLS 患者中发现了黏连蛋白调节因子 NIPBL 或黏连蛋白结构成分 SMC1A 和 SMC3 的杂合突变。黏连蛋白在有丝分裂和减数分裂期间调节姐妹染色单体的黏合。此外,黏连蛋白已被证明在基因表达调控中发挥关键作用。此外,黏连蛋白通路中的多种蛋白还参与其他基本的生物学事件,如双链 DNA 断裂修复、染色质重塑和维持基因组稳定性。在这里,我们将讨论黏连蛋白及其相关因子的生物学特性,并重点介绍 CdLS 的临床表现和与 CdLS 相关蛋白的机制研究。