Maternal homozygosity for the common MTHFR mutation as a potential risk factor for offspring with limb defects

A common mutation, C677T, in the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene leads to altered homocysteine metabolism, and has been associa ted with the occurrence of neural tube defects (NTD). Administration of fol ic acid decreases this risk. There is also evidence that periconceptional s upplementation of mothers with folic acid can decrease the risk of limb def ects in the offspring. Here we describe a child with a transverse terminal defect of one hand, whose mother is homozygous for the C677T MTHFR mutation . We suggest that homozygosity for the MTHFR mutation may be a risk factor for transverse terminal limb defect/s by an effect mediated through altered folate and homocysteine metabolism. Further studies of mothers of infants with limb reduction defects for the MTHFR mutation may be of help in establ ishing this association. A simple intervention in the form of folic acid su pplementation would be protective, should an association be established. (C ) 2001 Wiley-Liss,Inc.