Hypomethylation of GRHL3 gene is associated with the occurrence of neural tube defects.

AIM: To investigate the relationship between GRHL3 methylation and the etiology of neural tube defects (NTDs).

MATERIALS & METHODS: Analyze data from a genome-wide DNA methylation array. Targeted DNA methylation analysis was performed for 46 cases and 23 controls. At last, grhl3 overexpression and gene depletion experiments were conducted in zebrafish.

RESULTS: Five hypomethylated CpGs were discovered in the methylation arrays performed on NTD cases. In a validation study, 15 hypomethylated CpGs were found and the overall methylation levels decreased in brain/spinal cord tissue from NTD cases. The knockdown and overexpression of grhl3 in zebrafish damaged embryonic convergent extension processes.

CONCLUSION: Hypomethylation of GRHL3 in central nervous tissue is associated with NTDs, further supporting the importance of GRHL3 and methylation in proper neural tube closure.