Despite the limitations of our cohort small sample size and using a combination of biased and unbiased analytical approaches, we were able to (a) identify de novo variants that may play a role in severe forms of NTD (MMC and anencephaly) (Lemay et al., 2015); (b) implicate GRHL3 in the etiology of human NTD (Lemay et al., 2017); (c) identify LOF variants in orthologues of mouse NTD genes, including SHROOM3, DLC1, and ITGB1, in human NTD (the current study); and (d) identify MYO1E as a novel potential NTD candidate gene (current study). This evidence concerns the gene GRHL3 and neural tube defect.