Clinical and genetic analysis of idiopathic intellectual disability/development delay

Objective To diagnose etiologically about 30 children with idiopathic intellectual disability/deve-lopment delay(ID/DD) through clinical and genetic analysis. Methods Clinical data from 30 enrolled subjects were collected.Blood biochemical examination, screening for inherited metabolic disease, karyotype analysis, multiplex ligation-dependent probe amplification(MLPA), targeted next-generation sequencing (targeted NGS) and comprehensive chromosomal microarray analysis(CMA) were performed based on diagnosis flow process of etiology on ID/DD.The disease-causing variations were analyzed for genetic changes from ID/DD patients detected. Results Thirty subjects all obtained idiopathic ID/DD diagnosis according to ID/DD criteria.Congenital malformations and abnormal mental and behaviors were manifested in 40.0% (12/30 cases) and 26.7% (8/30 cases) patients, respectively.Genetic varia-tions were found in 29 patients (96.7%, 29/30 cases), in which disease-causing variations were confirmed from 8 patients, and 5 novel mutations from 4 genes [NFIX c. 613C>T (p.Q205X), DHCR7 c. 1376G>A (p.W459X) and c. 901C>A (p.H301N), UPF3B c. 1034G>A (p.R345H), DLG3 c. 128G>T (p.G43V)] were found.Eight patients were diagnosed genetically including one 22q13.3 deletion syndrome, one Angelman syndrome, one Sotos syndrome 2, one Smith-Lemli-Opitz syndrome, one 11q24.1q24.2 microduplication syndrome, one 15q21.3q22.2 microdeletion syndrome and two X-linked ID.Diagnosis rates of karyotype, MLPA, targeted NGS and CMA were 4.5% (1/22 cases), 6.7% (2/30 cases), 13.3% (4/30 cases) and 28.6% (2/7 cases), respectively. Conclusions Etiology diagnosis for 8 patients with ID/DD were identified, which expanded the mutation spectrums of NFIX, DHCR7, UPF3B, DLG3.This is the first report about disease-causing mutation in NFIX resulting in Sotos syndrome 2 in Chinese people. Key words: Intellectual disability; Development delay; Mutation; Next-generation sequencing; Chromosomal microarray analysis