典型文献
Loss-of-function of KMT5B leads to neurodevelopmental disorder and impairs neuronal development and neurogenesis
文献摘要：
Autism spectrum disorder(ASD)is a group of neurodevelopmental disorders that cause severe social,communication,and behavioral problems.Recent studies show that the variants of a histone methyl-transferase gene KMT5B cause neurodevelopmental disorders(NDDs),including ASD,and the knockout of Kmt5b in mice is embryonic lethal.However,the detailed genotype-phenotype correlations and functional effects of KMT5B in neurodevelopment are unclear.By targeted sequencing of a large Chinese ASD cohort,analyzing published genome-wide sequencing data,and mining literature,we curated 39 KMT5B variants identified from NDD individuals.A genotype-phenotype correlation analysis for 10 individuals with KMT5B pathogenic variants reveals common symptoms,including ASD,intellectual disability,languages problem,and macrocephaly.In vitro knockdown of the expression of Kmt5b in cultured mouse primary cortical neurons leads to a decrease in neuronal dendritic complexity and an increase in dendritic spine density,which can be rescued by expression of human KMT5B but not that of pathogenic de novo missense mutants.In vivo knockdown of the Kmt5b expression in the mouse embryonic cerebral cortex by in utero electroporation results in decreased proliferation and accelerated migration of neural progenitor cells.Our findings reveal essential roles of histone methyltransferase KMT5B in neuronal development,prenatal neurogenesis,and neuronal migration.
文献关键词：
中图分类号：
作者姓名：
Guodong Chen;Lin Han;Senwei Tan;Xiangbin Jia;Huidan Wu;Yingting Quan;Qiumeng Zhang;Bin Yu;Zhengmao Hu;Kun Xia;Hui Guo
作者机构：
Center of Medical Genetics,School of Life Sciences,Central South University,Changsha,Hunan 421001,China;Chongqing Reproductive and Genetics Institute,Chongqing Health Center for Women and Children,Chongqing 400010,China;CAS Center for Excellence in Brain Science and Intelligences Technology(CEBSIT),Chinese Academy of Sciences,Shanghai 200030,China;Hunan Key Laboratory of Animal Models for Human Diseases,Changsha,Hunan 410078,China
文献出处：
引用格式：
[1]Guodong Chen;Lin Han;Senwei Tan;Xiangbin Jia;Huidan Wu;Yingting Quan;Qiumeng Zhang;Bin Yu;Zhengmao Hu;Kun Xia;Hui Guo-.Loss-of-function of KMT5B leads to neurodevelopmental disorder and impairs neuronal development and neurogenesis)[J].遗传学报,2022(09):881-890
A类：
KMT5B,Kmt5b,macrocephaly
B类：
Loss,leads,neurodevelopmental,impairs,neuronal,neurogenesis,Autism,spectrum,ASD,group,disorders,that,cause,severe,social,communication,behavioral,problems,Recent,studies,show,variants,histone,NDDs,including,knockout,mice,embryonic,lethal,However,detailed,genotype,phenotype,correlations,functional,effects,are,unclear,By,targeted,sequencing,large,Chinese,cohort,analyzing,published,genome,wide,data,mining,literature,curated,identified,from,individuals,analysis,pathogenic,reveals,common,symptoms,intellectual,disability,languages,In,vitro,knockdown,expression,cultured,mouse,primary,cortical,neurons,dendritic,complexity,increase,spine,density,which,can,rescued,by,human,but,novo,missense,mutants,vivo,cerebral,cortex,utero,electroporation,results,decreased,proliferation,accelerated,migration,neural,progenitor,cells,Our,findings,essential,roles,methyltransferase,prenatal
AB值：
0.540078
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