PDF(Pubmed)
Abstract：
Individuals affected with autism often suffer additional co-morbidities such as intellectual disability. The genes contributing to autism cluster on a relatively limited number of cellular pathways, including chromatin remodeling. However, limited information is available on how mutations in single genes can result in such pleiotropic clinical features in affected individuals. In this review, we summarize available information on one of the most frequently mutated genes in syndromic autism the Activity-Dependent Neuroprotective Protein (ADNP).
Heterozygous and predicted loss-of-function ADNP mutations in individuals inevitably result in the clinical presentation with the Helsmoortel-Van der Aa syndrome, a frequent form of syndromic autism. ADNP, a zinc finger DNA-binding protein has a role in chromatin remodeling: The protein is associated with the pericentromeric protein HP1, the SWI/SNF core complex protein BRG1, and other members of this chromatin remodeling complex and, in murine stem cells, with the chromodomain helicase CHD4 in a ChAHP complex. ADNP has recently been shown to possess R-loop processing activity. In addition, many additional functions, for instance, in association with cytoskeletal proteins have been linked to ADNP.
We here present an integrated evaluation of all current aspects of gene function and evaluate how abnormalities in chromatin remodeling might relate to the pleiotropic clinical presentation in individual\"s\" with Helsmoortel-Van der Aa syndrome.
Heterozygous and predicted loss-of-function ADNP mutations in individuals inevitably result in the clinical presentation with the Helsmoortel-Van der Aa syndrome, a frequent form of syndromic autism. ADNP, a zinc finger DNA-binding protein has a role in chromatin remodeling: The protein is associated with the pericentromeric protein HP1, the SWI/SNF core complex protein BRG1, and other members of this chromatin remodeling complex and, in murine stem cells, with the chromodomain helicase CHD4 in a ChAHP complex. ADNP has recently been shown to possess R-loop processing activity. In addition, many additional functions, for instance, in association with cytoskeletal proteins have been linked to ADNP.
We here present an integrated evaluation of all current aspects of gene function and evaluate how abnormalities in chromatin remodeling might relate to the pleiotropic clinical presentation in individual\"s\" with Helsmoortel-Van der Aa syndrome.
摘要：
背景：患有自闭症的个体通常会遭受其他合并症，例如智力障碍。导致自闭症的基因聚集在数量相对有限的细胞通路上，包括染色质重塑。然而,关于单基因突变如何在受影响的个体中导致这种多效性临床特征的信息有限.在这次审查中,我们总结了有关综合征性自闭症中最常见突变基因之一的现有信息，即活动依赖性神经保护蛋白（ADNP）。
结果：个体中的杂合和预测的功能丧失ADNP突变不可避免地导致Helsmoortel-VanderAa综合征的临床表现，一种常见的综合征性自闭症。ADNP,锌指DNA结合蛋白在染色质重塑中起作用：该蛋白与着丝粒周围蛋白HP1，SWI/SNF核心复合物蛋白BRG1以及该染色质重塑复合物的其他成员相关，在鼠干细胞中，ChAHP复合物中的色域解旋酶CHD4。最近已显示ADNP具有R环处理活性。此外,许多附加功能，例如,与细胞骨架蛋白相关的ADNP。
结论：我们在此对当前基因功能的所有方面进行了综合评估，并评估了染色质重塑异常与Helsmoortel-VanderAa综合征患者的多效性临床表现之间的关系。
结果：个体中的杂合和预测的功能丧失ADNP突变不可避免地导致Helsmoortel-VanderAa综合征的临床表现，一种常见的综合征性自闭症。ADNP,锌指DNA结合蛋白在染色质重塑中起作用：该蛋白与着丝粒周围蛋白HP1，SWI/SNF核心复合物蛋白BRG1以及该染色质重塑复合物的其他成员相关，在鼠干细胞中，ChAHP复合物中的色域解旋酶CHD4。最近已显示ADNP具有R环处理活性。此外,许多附加功能，例如,与细胞骨架蛋白相关的ADNP。
结论：我们在此对当前基因功能的所有方面进行了综合评估，并评估了染色质重塑异常与Helsmoortel-VanderAa综合征患者的多效性临床表现之间的关系。
