OBJECTIVE: To explore the application of gene microarray combined with whole exome sequencing (WES) in prenatal diagnosis of fetal nervous system (NS) malformation. STUDY DESIGN: Two fetal tissues were taken for lowcoverage WES combined with bioinformatics analysis. RESULTS: We found that in the simple NS malformation group, chromosomal abnormalities were detected in 3 cases by conventional karyotyping and 8 cases by gene microarray, increasing the detection rate by 10.0%. In the NS malformation combined with other malformations group, conventional karyotyping showed abnormalities in 5 cases, while gene microarray detected abnormalities in 9 cases, increasing the detection rate by 11.7%. In addition, there were 3 cases with normal karyotype and gene microarray, but 2 cases of those with abnormalities were detected by WES. CONCLUSION: Gene microarray can improve the detection rate of fetal NS malformations. When combined with WES, it significantly increases the detection rate of chromosomal abnormalities of NS malformation. © Science Printers and Publishers, Inc.