Methyl-CpG-binding protein 2 （MeCP2） is a classic methylated-DNA-binding protein, dysfunctions of which lead to various neurodevelopmental disorders such as Rett syndrome and autism spectrum disorder. Initially reco...Methyl-CpG-binding protein 2 （MeCP2） is a classic methylated-DNA-binding protein, dysfunctions of which lead to various neurodevelopmental disorders such as Rett syndrome and autism spectrum disorder. Initially recognized as a transcriptional repressor, MeCP2 has been studied extensively and its functions have been expanded dramatically in the past two decades. Recently, it was found to be involved in gene regulation at the post-transcriptional level. MeCP2 represses nuclear microRNA processing by interacting directly with the Drosha/DGCR8 complex. In addition to its multifaceted functions, MeCP2 is remarkably modulated by post- translational modifications such as phosphorylation, SUMOylation, and acetylation, providing more regulatory dimensions to its functions. The role of MeCP2 in the central nervous system has been studied extensively, from neurons to glia. Future investigations combining molecular, cellular, and physiological methods are necessary for defining the roles of MeCP2 in the brain and developing efficient treatments for MeCP2-related brain disorders.展开更多
目的通过对甲基化CpG结合蛋白2(mehty1-Cp G binding protein 2,MECP2)基因的突变分析,对1例典型的Rett综合征患儿进行基因诊断,并为该家庭提供遗传咨询。方法采用聚合酶链反应和DNA直接测序对先证者及其父母MECP2基因的4个外显子进行...目的通过对甲基化CpG结合蛋白2(mehty1-Cp G binding protein 2,MECP2)基因的突变分析,对1例典型的Rett综合征患儿进行基因诊断,并为该家庭提供遗传咨询。方法采用聚合酶链反应和DNA直接测序对先证者及其父母MECP2基因的4个外显子进行序列分析,同时对患儿进行染色体核型分析以排除染色体异常。结果患儿核型正常。针对MECP2基因进行突变分析发现患者存在c.473C>T(T158M)杂合突变,其父母未检测到该突变。结论错义突变T158M是导致该RETT家系患者临床表型的主要原因,通过对RETT家系个体Mecp2基因分析可对REET家系进行有效的遗传咨询。展开更多
Autism spectrum disorder（ASD） encompasses a complex set of developmental neurological disorders,characterized by de？cits in social communication and excessive repetitive behaviors. In recent years, ASD is increasin...Autism spectrum disorder（ASD） encompasses a complex set of developmental neurological disorders,characterized by de？cits in social communication and excessive repetitive behaviors. In recent years, ASD is increasingly being considered as a disease of the synapse.One main type of genetic aberration leading to ASD is gene duplication, and several mouse models have been generated mimicking these mutations. Here, we studied the effects of MECP2 duplication and human chromosome15q11-13 duplication on synaptic development and neural circuit wiring in the mouse sensory cortices. We showed that mice carrying MECP2 duplication had speci？c defects in spine pruning, while the 15q11-13 duplication mouse model had impaired spine formation. Our results demonstrate that spine pathology varies signi？cantly between autism models and that distinct aspects of neural circuit development may be targeted in different ASD mutations.Our results further underscore the importance of gene dosage in normal development and function of the brain.展开更多
基金supported by the National Basic Research Development Program of China (2011CBA00400)the Strategic Priority Research Program of the Chinese Academy of Science,China (XDB02050400)
文摘Methyl-CpG-binding protein 2 （MeCP2） is a classic methylated-DNA-binding protein, dysfunctions of which lead to various neurodevelopmental disorders such as Rett syndrome and autism spectrum disorder. Initially recognized as a transcriptional repressor, MeCP2 has been studied extensively and its functions have been expanded dramatically in the past two decades. Recently, it was found to be involved in gene regulation at the post-transcriptional level. MeCP2 represses nuclear microRNA processing by interacting directly with the Drosha/DGCR8 complex. In addition to its multifaceted functions, MeCP2 is remarkably modulated by post- translational modifications such as phosphorylation, SUMOylation, and acetylation, providing more regulatory dimensions to its functions. The role of MeCP2 in the central nervous system has been studied extensively, from neurons to glia. Future investigations combining molecular, cellular, and physiological methods are necessary for defining the roles of MeCP2 in the brain and developing efficient treatments for MeCP2-related brain disorders.
文摘目的通过对甲基化CpG结合蛋白2(mehty1-Cp G binding protein 2,MECP2)基因的突变分析,对1例典型的Rett综合征患儿进行基因诊断,并为该家庭提供遗传咨询。方法采用聚合酶链反应和DNA直接测序对先证者及其父母MECP2基因的4个外显子进行序列分析,同时对患儿进行染色体核型分析以排除染色体异常。结果患儿核型正常。针对MECP2基因进行突变分析发现患者存在c.473C>T(T158M)杂合突变,其父母未检测到该突变。结论错义突变T158M是导致该RETT家系患者临床表型的主要原因,通过对RETT家系个体Mecp2基因分析可对REET家系进行有效的遗传咨询。
基金supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences,China(XDB02010000)the National Natural Science Foundation of China(31530030 and 81371270)the Science and Technology Commission of Shanghai Municipality,China(16XD1404800)
文摘Autism spectrum disorder（ASD） encompasses a complex set of developmental neurological disorders,characterized by de？cits in social communication and excessive repetitive behaviors. In recent years, ASD is increasingly being considered as a disease of the synapse.One main type of genetic aberration leading to ASD is gene duplication, and several mouse models have been generated mimicking these mutations. Here, we studied the effects of MECP2 duplication and human chromosome15q11-13 duplication on synaptic development and neural circuit wiring in the mouse sensory cortices. We showed that mice carrying MECP2 duplication had speci？c defects in spine pruning, while the 15q11-13 duplication mouse model had impaired spine formation. Our results demonstrate that spine pathology varies signi？cantly between autism models and that distinct aspects of neural circuit development may be targeted in different ASD mutations.Our results further underscore the importance of gene dosage in normal development and function of the brain.
