Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of Cornelia de Lange syndrome with predominant mental retardation
Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of Cornelia de Lange syndrome with predominant mental retardation
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DOI：
10.1086/511888
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发表时间：
2007-03-01
影响因子：
9.8
通讯作者：
Krantz, Ian D.
中科院分区：
文献类型：
--
作者：
Deardorff, Matthew A.;Kaur, Maninder;Krantz, Ian D.
内聚蛋白调节因子NIPBL和ESCO 2的突变分别导致科尔内利亚德兰格综合征（CdLS）和罗伯茨或SC短肢畸形综合征。最近，突变的cohesin复合物结构组件SMC1A已被确定在两个先证者与功能的CdLS。在这里，我们报告的识别的基因编码的互补亚基的粘附素异源二聚体，SMC 3，和14个额外的SMC 1A突变的突变。预测所有突变保留开放阅读框，并且未鉴定出截短突变。突变体SMC3和SMC1A蛋白的结构分析表明，所有可能产生的功能性粘着蛋白复合物，但我们认为，他们可能会改变他们的染色体结合动力学。我们的数据表明，SMC3和SMC1A突变（1）导致约5%的CdLS病例，（2）导致持续的轻度表型，缺乏与CdLS典型相关的主要结构异常，（3）在某些情况下，导致接近明显非综合征性精神发育迟滞的表型。
Mutations in the cohesin regulators NIPBL and ESCO2 are causative of the Cornelia de Lange syndrome (CdLS) and Roberts or SC phocomelia syndrome, respectively. Recently, mutations in the cohesin complex structural component SMC1A have been identified in two probands with features of CdLS. Here, we report the identification of a mutation in the gene encoding the complementary subunit of the cohesin heterodimer, SMC3, and 14 additional SMC1A mutations. All mutations are predicted to retain an open reading frame, and no truncating mutations were identified. Structural analysis of the mutant SMC3 and SMC1A proteins indicate that all are likely to produce functional cohesin complexes, but we posit that they may alter their chromosome binding dynamics. Our data indicate that SMC3 and SMC1A mutations ( 1) contribute to similar to 5% of cases of CdLS, ( 2) result in a consistently mild phenotype with absence of major structural anomalies typically associated with CdLS, and ( 3) in some instances, result in a phenotype that approaches that of apparently nonsyndromic mental retardation.