The single nucleotide polymorphism (SNP) of the vangl1 gene is highly correlated with Neural Tube Defects (NTDs), a group of severe congenital malformations.
We identified three heterozygous missense variants in VANGL1, p.Ala187Val, p.Asp389His, and p.Arg517His, that are absent in controls and predicted to be detrimental on the protein function and, thus, we expanded the mutational spectrum of VANGL1 in NTD cases.
Of interest are two arginine residues, R181 and R274, that are highly conserved in Vangl protein homologues and found to be independently mutated in VANGL1 (R181Q and R274Q) and VANGL2 (R177H and R270H) in human cases of NTDs.
In 48 children with a neural tube defect and 62 controls from a Dutch case-control study and 34 children with a neural tube defect and 78 controls from a Texan case-control study, we measured the DNA-methylation levels of imprinted candidate genes (IGF2-DMR, H19, KCNQ1OT1) and non-imprinted genes (the LEKR/CCNL gene region associated with birth weight, and MTHFR and VANGL1 associated with NTD).