Abstract
Although more than 200 genes are known to be related to neural tube defects (NTDs), the exact molecular basis is still unclear. Evaluating the contribution of copy number variation (CNV) might be a priority because CNV involves changes in the copy number of large segments of DNA, leading to phenotypic traits and disease susceptibility. Recent studies have documented that the polarity protein partitioning defective 3 homolog (Pard3) plays an essential role in the process of neural tube closure. The aim of this study was to assess the role of PARD3 CNVs in the etiology of human NTDs. Relative quantitative PCR and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were used to quantitative measurement of CNVs in 25 PARD3 exons in 202 NTD cases and 231 controls from a region of China with a high prevalence of NTDs. The results showed that microduplications ranging from 3 to 4 were evident in coding Exon 21 and Exon 25 in both case and control groups. A novel heterozygous microdeletion spanning 444 bp of Exon 14 was identified in two cases of anencephaly and is absent from all controls analyzed. Expression analyses indicated that this heterozygotic microdeletion showed no tissue specificity and led to defective expression of PARD3. Our study provides further evidence implicating PARD3 in the etiology of NTDs.