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 China.Methods:We evaluated 1051 ID/GDD children aged 6 months to 18 years from March 2009 to April 2017.Data concerning basic clinical manifestations were collected,and the method of etiology confirmation was recorded.Genome-wide copy number variations (CNVs) detection and high-throughput sequencing of exons in the targeted regions was performed to identify genetically-based etiologies.We 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 test.Results:We recruited 1051 children with mild (367,34.9％),moderate (301,28.6％),severe (310,29.5％),and profoundly severe (73,6.9％) ID/GDD.The 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 mutation.We 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 (x2=12.645,P ＜ 0.001).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 in X-linked genes (cyclin-dependent kinase like 5,protocadherin 19,IQ motif and Sec7 domain 2,and methyl-CpG binding protein 2) were reported in the study.Conclusions:The present study indicates that genetic analysis is an effective method to increase the proportion of confirmed etiology in ID/GDD children and is highly recommended,especially in ID/GDD children with uncertain etiology.