Clinical application of CNV-Seq in the diagnosis of children with abnormal brain development in 130 cases

Background To evaluate the diagnostic value of applying genome copy number variation sequencing (CNV-seq) in the genetic etiology of abnormal brain development (ABD). Methods We selected 130 ABD patients discovered in Gansu Maternal and Child Health Hospital from December 2018 to October 2023 as the research subjects, divided into non-syndrome ABD group and syndrome ABD group, performed CNV-seq testing and analyzed the genetic causes of copy number variation. Results In the 130 cases, we detected a total of 42 abnormal samples, with an abnormal detection rate of 32.3%, included 3 cases (2.3%) of aneuploidy and 39 cases (30%) of CNVs; of which 15 cases were detected in the non-syndrome ABD group, included 1 case (6.67%, 1/15) of aneuploidy, 4 cases (26.7%，4/15) of pathogenic CNVs (pCNVs) and 10 case (66.7%，10/15) of variant of uncertain significance (VUS), and 27 cases were detected in the syndrome-type ABD group, including 2 cases (7.4%, 2/27) of aneuploidy, 19 cases (70.4%, 19/27) of pCNVs and 6 cases (22.2%, 6/27) of VUS. Chi-square test suggested that the difference in detection rate was statistically significant (P<0.05). Conclusion In current study, the application of CNV-Seq in all ABD patient groups has a high abnormal detection rate, especially in the population of syndrome ABD, the detection rate was higher than that of non-syndrome ABD, but in the population of non-syndrome ABD patients, due to the low positive detection rate and the lack of obvious clinical phenotypes, such population were more likely to be neglected in clinical practice. Accordingly, more attention should be paid to population with non-syndrome ABD. In addition, prenatal diagnosis and genetic counseling should be performed in a timely manner for these of patients.