Genome-wide Copy Number Variations Analysis In 31 Patients With Unexplained Intellectual Disability/Developmental Delay

Objective:Unexplained intellectual/developmental disabilities(ID/DD) are common disabling diseases in development of the children, with complex etiologies, a varity of clinical manifestaions and high morbidity, leading to heavy burden to children and their families. Applying the Array-based Comparative Genomic Hybridization(Array-CGH) to detected the genome-wide copy number variations(CNVs) in patients with unexplained DD/ID. Analysing the relationship between CNVs and DD/ID and exploring the origin of pCNVs, we can provide the theoretical basis for genetic counseling and prenatal diagnosis. Methods:Based on inclusion criteria, a total of 31 patients with unexplained ID/DD were recruited from the children who visited the Peking University First Hospital Pediatric neurology clinics from November 2014 to October 2015. Getting the preparation of gDNA from peripheral blood from the patients and their parents. The gDNA from patients were detected to observe the chromosomal genomic copy number variation by Array-CGH, then the results were compared the CNVs datas of Genomic Variants(DGV), Decipher database, Online Mendelian Inheritance in Man(OMIM) and Pubmed to determine the pathogenicity of CNVs. The pCNVs were validated and explored the family investigation.Results:In this study, we have collected 31 patients with unexplained ID/DD, and 7 pCNVs were found in 6 patients(19.3%), involving four syndrome, which were respectively 1p36 deletion comprehensive syndrome, 22q11.2 deletion syndrome, Pitt-Hopkins syndrome(PTHs) and NRXN1 microdeletion syndrome. In addition, we have found 3 new pCNVs, which were heterozygous deletion locating on 3p26.3p26.2, 11q22.3q25 and 15q21.3-q22.2 respectively. Conclusion:Genomic pCNVs is one of the major genetic etiology of unexplained ID/DD patients, whose positive detection rate is 15%-20% by Array-CGH. In this study, the results showed etiological diagnosis of unexplained ID/DD was 19.3%(6/31) which was related to pCNVs through Array-CGH technologies, providing the theoretical basis for genetic counseling and prenatal diagnosis. We also found 3 new pCNVs, which provide clues to the discovery of the new syndrome. As high-throughput techniques, Array-CGH provide fast and effective etiological diagnosis for unexplained ID/DD, so they are worthy to be promoted.