The Relationship Between Chromosomal Copy Number Variations And Unexplained Intellectual Disability/Global Developmental Delay In Etiology

Object: To discuss the relationship between chromosomal copy number variations and unexplained intellectual disability or global developmental delay,and to explore the value of Next Generation Sequencing for identifying the etiology of unexplained intellectual disability or global developmental delay.Method:Peripheral blood samples from unexplained ID/GDD patients were analyzed with Next Generation Sequencing technique using Next Seq CN 500 high-throughput sequencer.The results were analyzed by RUPA rapid comparison method which is completely matched with the human genome.Results:In the total enrolled 587 children with unexplained ID/GDD,age ranged from 4months to 9 years and 7 months.There were more males than females(1.7: 1),with slightly less urban residents than in rural areas(1: 1.2),abnormal pregnancy and abnormal birth process showed statistical significance(P<0.05))One hundred eighteen cases(20.1%)were detected with abnormalities,among which 32 cases were diagnosed with microdeletion/microduplication syndromes.These included five Williams-Beuren syndromes,four Prader-Willi /Angelman syndromes,two Phelan-Mcdermid syndromes and two 22q11 deletion syndromes.In addition,9 cases were diagnosed with potentially pathogenic copy number variations(pp CNV).In 118 cases,50 of them had detected pathogenic genes,36 of them was suspected as variants of unknown significance.half of their parents carried out NGS.The results showed that 13 cases were inherited from one of the phenotypically normal parents,5 cases were de novo.Conclusion:The ID/GDD with unknown reason is highly related to genetic disorders.A variety of genetic mutations,especially copy number variations.NGS is an effective method for identifying the etiology of ID/GDD and is capable of identifying microdeletion/mieroduplication syndromes as well as de novo pathogenic CNVs which may be missed by conventional karyotyping.Based on the results,candidate genes for ID/GDD may be identiffed.