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

• Published in: Chinese medical journal 2019-07, Vol.132 (13), p.1533-1540
• Main Authors: Liao, Li-Hong, Chen, Chen, Peng, Jing, Wu, Li-Wen, He, Fang, Yang, Li-Fen, Zhang, Ci-Liu, Wang, Guo-Li, Peng, Pan, Ma, Yu-Ping, Miao, Pu, Yin, Fei
• Format: Article
• Language: English
• Subjects: Adolescent; Child; Child, Preschool; China; DNA Copy Number Variations - genetics; Electroencephalography; Etiology; Female; Genetic Testing; Genomes; Humans; Infant; Infant, Newborn; Intellectual disabilities; Intellectual Disability - genetics; Intelligence tests; Male; Mass spectrometry; Medical imaging; Metabolic disorders; Mutation; Mutation - genetics; Original; Scientific imaging; Statistical analysis
• ISSN: 0366-6999; 2542-5641
• DOI: 10.1097/CM9.0000000000000295

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. 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. 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 (χ = 12.645, P