Is There a Reason for MTHFR C677T Variant Testing in Fetuses with Anencephaly?

Abstract This study investigated the association between the fetal MTHFR C677T variant (rs1801133, NC_000001.11:g.11796321G > A) and anencephaly risk in Slovak population. Anencephaly represents a prenatally or perinatally fatal malformation, therefore genetic examinations often have to be made in a post mortem setting. While the MTHFR C677T TT genotype has been implicated as a risk factor for neural tube defects, including anencephaly, its contribution remains uncertain. Archived tissue samples (predominately chorionic villi) from 20 anencephaly cases, where post mortem genetic evaluation was requested, were genotyped for the MTHFR C677T variant using technique based on restriction fragment length polymorphism and confirmed by droplet digital PCR. Control genotype frequencies were obtained from a previously published study of 534 healthy Slovak adults by Sutovsky et al. The genotype distribution in the anencephaly cases was: CC (40%), CT (55%), and TT (5%). Within the limits of this small case series, no statistically significant association was observed between fetal MTHFR C677T genotype and anencephaly.. These findings indicate that MTHFR C677T genotyping alone provides limited etiological insight in post-mortem investigations of anencephaly. Larger, adequately powered studies incorporating comprehensive genetic analyses will be necessary to clarify the role of genetic factors contributing to anencephaly in this population.