Targeted sequencing and integrative analysis of 3,195 Chinese patients with neurodevelopmental disorders prioritized 26 novel candidate genes

作     者：Tao Wang Yi Zhang Liqui Liu Yan Wang Huiqian Chen Tianda Fan Jinchen Li Kun Xia Zhongsheng Sun Tao Wang;Yi Zhang;Liqui Liu;Yan Wang;Huiqian Chen;Tianda Fan;Jinchen Li;Kun Xia;Zhongsheng Sun

作者机构：Center for Medical Genetics&Hunan Key Laboratory of Medical GeneticsSchool of Life SciencesCentral South UniversityChangshaHunan 410083China Beijing Institutes of Life ScienceChinese Academy of SciencesBeijing 100101China DIAGenes Precision MedicineBeijing 102600China National Clinical Research Centre for Geriatric DisordersDepartment of GeriatricsXiangya HospitalCentral South UniversityChangshaHunan 410083China Shanghai Adeptus BiotechnologyShanghai 200126China Institute of Genomic MedicineWenzhou Medical UniversityWenzhouZhejiang 325035China Department of NeurologyXiangya HospitalCentral South UniversityChangsha Hunan410083China CAS Center for Excellence in Brain Science and Intelligences Technology(CEBSIT)Shanghai 200031China School of Basic Medical ScienceCentral South UniversityChangshaHunan410083China CAS Center for Excellence in Biotic InteractionsUniversity of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Integrated Management of Pest Insects and RodentsChinese Academy of SciencesBeijing 100101China 

出 版 物：《Journal of Genetics and Genomics》 (遗传学报（英文版）)

年 卷 期：2021年第48卷第4期

页      面：312-323页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：supported by the Guangdong Key Project in“Development of new tools for diagnosis and treatment of Autism”(2018B030335001 to Z.Sun)and“Early diagnosis and treatment of autism spectrum disorders”(202007030002 to Z.Sun) the National Natural Science Foundation of China(32070590 to Y.Wang) the National Natural Science Foundation of China(81730036 and81525007 to K.Xia) Science and Technology Major Project of Hunan Provincial Science and Technology Department(2018SK1030 to K.Xia) the National Natural Science Foundation of China(81801133 to J.Li) the Young Elite Scientist Sponsorship Program by CAST(2018QNRC001 to J.Li) the Innovation-Driven Project of Central South University(20180033040004 to J.Li) Natural Science Foundation of Hunan Province for outstanding Young Scholars(2020JJ3059 to J.Li) 

主　　题：De novo mutations X-linked variants Rare inherited variants Homozygous mutations Neurodevelopmental disorders Autism spectrum disorders Candidate genes 

摘      要：Neurodevelopmental disorders(NDDs)are a set of complex disorders characterized by diverse and cooccurring clinical *** genetic contribution in patients with NDDs remains largely ***,we sequence 519 NDD-related genes in 3,195 Chinese probands with neurodevelopmental phenotypes and identify 2,522 putative functional mutations consisting of 137 de novo mutations(DNMs)in 86 genes and 2,385 rare inherited mutations(RIMs)with 22 X-linked hemizygotes in 13 genes,2 homozygous mutations in 2 genes and 23 compound heterozygous mutations in 10 ***,the DNMs of16,807 probands with NDDs are retrieved from public datasets and combine in an integrated analysis with the mutation data of our Chinese NDD probands by taking 3,582 in-house controls of Chinese origin as *** prioritize 26 novel candidate ***,six of these genes d ITSN1,UBR3,CADM1,RYR3,FLNA,and PLXNA3 d preferably contribute to autism spectrum disorders(ASDs),as demonstrated by high co-expression and/or interaction with ASD genes confirmed via rescue experiments in a mouse ***,these genes are differentially expressed in the ASD cortex in a significant manner and involved in ASD-associated ***,our study expands the genetic spectrum of Chinese NDDs,further facilitating both basic and translational research.