XU Chenyang,XIANG Yanbao,ZHOU Lili, et al. Clinical application of chromosomal microarray analysis in the diagnosis of fetal central nervous systemmalformations[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2024, 54(2): 112-119.
Abstract：Objective: To assess chromosomal variations in 232 fetuses diagnosed with central nervous system (CNS) malformations and explore the relationship between genotype and phenotype. Methods: By chromosomal microarray analysis (CMA) and karyotyping, 232 fetuses with CNS malformations diagnosed by prenatal imaging in Wenzhou Central Hospital from 2014 to 2022 were screened for chromosomal variations. The pathogenicity of the detected variations was evaluated and the detection rates across different CNS malformation types was analyzed was analyzed. Results: The results revealed that the detection rate for chromosomal karyotype abnormalities was 9.1% (19/209), while the overall chromosomal abnormality detection rate using CMA was 22.8% (53/232). These abnormalities included one case of polyploid(1/232, 0.4%), 19 cases of aneuploidy(19/232, 8.2%), and 33 other pathogenic or likely pathogenic copy number variations (CNVs) (33/232, 14.2%).The CNVs involved 12 types of microdeletion/microduplication syndromes, uniparental disomy of chromosome 14, and several dosage-sensitive genes, including DLL1, FOXC1, SHH, ZIC2, and CHAMP1. Furthermore, fetuses with non-isolated CNS malformations had a higher rate of pathogenic variations than those with isolated CNS anomalies, and the difference was statistically significant (47.4% vs. 14.9%, P<0.01). Conclusion: In conclusion,CMA is a rapid and reliable technique for detecting CNVs associated with CNS malformations. Research on the correlation between CNS phenotype and genotype is vital for the prevention and control of congenital disabilities and pathogenic mechanisms.
