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Background Neural tube defects(NTDs)are one of the most common birth defects caused by a combination of genetic and environmental factors.Currently,little is known about the genetic basis of NTDs although up to 70% of human NTDs were reported to be attributed to genetic factors.Here we performed a genome-wide copy number variant(CNV)detection in a cohort of Chinese NTD patients in order to exam the potential role of CNV in the pathogenesis of NTDs.Methods The genomic DNA from Eighty-five NTD cases and seventy-five normal controls were subjected for whole genome copy number analysis using Agilent 244K CGH array.Non-DGV(the Database of Genomic Variants)CNVs from each group were further analyzed for their associations with NTDs.Gene content in non-DGV CNVs as well as participating pathways were analyzed.Results Fifty-five and twenty-six non-DGV CNVs were detected in case and control respectively,among them,forty and nineteen CNVs involve genes(genic CNV).Significantly more non-DGV and non-DGV genic CNV were detected in NTD patients than in control(41.2% vs.25.3%,p<0.05 and 37.6% vs.20%,p<0.05).Non-DGV genic CNVs are associated with a 2.65-fold increased risk for NTDs(95% CI:1.24-5.87).Interestingly,there are 41 cilia genes involved in non-DGV CNVs from NTD patients which is significantly enriched in cases compared with that in control(24.7% vs.9.3%,p<0.05),resulting in 3.19-fold increased risk for NTDs(95% CI:1.27-8.01).Pathway analyses further suggested that tight junction signaling and protein kinase A signaling are top canonical pathways implicated in NTD-specific CNVs,and these two novel pathways interact with known NTD pathways.Conclusions Evidence from the CNV study suggests that genomic imbalance involving cilia genes are associated with NTD.Tight junction signaling and protein kinase Asignaling pathways are important in NTD pathogenesis.