Genetics Research On Children’s Intellectual Disability

Objective:In this study,we applied chromosome karyotype,low-depth wholegenome copy number variation sequencing(CNV-seq),and whole-exome sequencing(WES)to 38 cases of unexplained intellectual disability.(Intellectual disability,ID)/Global developmental delay(DD)patients are tested,aiming to: 1)Explore the genetic etiology of patients with unexplained ID/DD at the chromosome,genome,and single gene levels,in order to explore ID Provide data support for the pathogenic mechanism of /DD;2)Improve the diagnosis rate of ID/DD by analyzing the advantages and disadvantages of the three detection technologies;3)Provide basis for consultation,prenatal diagnosis,recurrence risk assessment and fertility guidance,thereby reducing the birth rate of children with ID/DD and improving the quality of the population in our district.Methods: For 38 patients diagnosed with unexplained ID/DD,after the family members signed the informed consent,6ml of the patient’s peripheral blood was collected,and chromosome karyotype analysis was performed to detect the number of chromosomes and large structural abnormalities(>5MB);For those undiagnosed by type analysis,CNV-seq analysis is performed to detect microdeletions and microduplications at the patient’s genome level;for those who are still undiagnosed by CNV-seq,WES analysis is performed to detect the patient’s single-gene mutations to find the genetic disease factor.Results: 1)After karyotype analysis of 38 unexplained ID/DD samples,a total of 10 patients with abnormal karyotypes were detected,including 8 abnormal numbers and 2 structural abnormalities;8 abnormal numbers including 21-trisomy There were 6 cases of symptoms,1 case of Turner syndrome,1 case of super-female syndrome,all of which were pathogenic,and the diagnosis rate was 21.05%(8/38).2)CNV-seq analysis was performed on 30 ID/DD samples with undiagnosed chromosomal karyotypes.A total of 11 abnormal results were detected,5 of which were pathogenic CNV,which increased the diagnosis rate to34.21%(13/38),And the remaining 6 cases had unclear clinical significance.3)WES was performed on 25 samples with undiagnosed chromosomal karyotype and CNV-seq.Only 1 case can explain the cause of ID/DD in the proband.The mutant gene is GRIN2 A,so the final diagnosis is the combined use of the three methods The rate was 36.84%(14/38).Conclusion: Through the comprehensive use of chromosome karyotype,CNV-seq and WES three technologies,the diagnosis rate of ID/DD patients has been significantly improved,which not only enriches the ID/DD variant spectrum,but more importantly,clarifies the causes of these patients.It is helpful for genetic counseling and prenatal diagnosis of the family.