Diagnosis of intellectual disability/global developmental delay via genetic analysis in a central region of China

作     者：Li-Hong Liao Chen Chen Jing Peng Li-Wen Wu Fang He Li-Fen Yang Ci-Liu Zhang Guo-Li Wang Pan Peng Yu-Ping Ma Pu Miao Fei Yin 

作者机构：Department of PediatricsXiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Intellectual and Developmental Disabilities Research CenterChangshaHunan 410008China Department of PediatricsZhongnan Hospital of Wuhan UniversityWuhan UniversityWuhanHubei 430071China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2019年第132卷第13期

页      面：1533-1540页

核心收录：

学科分类：10[医学] 

基　　金：grants from the National Natural Science Foundation of China(No.81771408,No.81771409,and No.81300555) the National Key Research and Development Program of China(No.2016YFC1306202) 

主　　题：Intellectual disability Global developmental delay Children Gene analysis Etiology 

摘      要：Background:Advanced technology has become a valuable tool in etiological studies of intellectual disability/global developmental delay(ID/GDD).The present study investigated the role of genetic analysis to confirm the etiology in ID/GDD patients where the cause of the disease was uncertain in central ***:We evaluated 1051 ID/GDD children aged 6 months to 18 years from March 2009 to April *** concerning basic clinical manifestations were collected,and the method of etiology confirmation was ***-wide copy number variations(CNVs)detection and high-throughput sequencing of exons in the targeted regions was performed to identify genetically-based *** compared the incidence of different methods used to confirm ID/GDD etiology among groups with differing degrees of ID/GDD using the Chi-square or Fisher exact probability ***:We recruited 1051 children with mild(367,34.9%),moderate(301,28.6%),severe(310,29.5%),and profoundly severe(73,6.9%)ID/*** main causes of ID/GDD in the children assessed were perinatal factors,such as acquired brain injury,as well as single gene imbalance and chromosomal gene *** identified karyotype and/or CNVs variation in 46/96(47.9%)of cases in severe ID/GDD patients,which was significantly higher than those with mild and moderate ID/GDD of 34/96(35.4%)and 15/96(15.6%),respectively.A total of 331/536(61.8%)patients with clear etiology have undergone genetic analysis while 262/515(50.9%)patients with unclear etiology have undergone genetic analysis(x^2=12.645,P0.001).Gene structure variation via karyotype analysis and CNV detection increased the proportion of children with confirmed etiology from 51.0%to 56.3%,and second-generation high-throughput sequencing dramatically increased this to 78.9%.Ten novel mutations were detected,recessive mutations in X-linked genes(ATPase copper transporting alpha and bromodomain and WD repeat domain containing 3)and dominant de novo heterozygous mutations i