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J Med Genet 39:368-369 doi:10.1136/jmg.39.5.368
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Maternal MTHFR genotype contributes to the risk of non-syndromic cleft lip and palate

  1. N J Prescott,
  2. R M Winter,
  3. S Malcolm
  1. Clinical and Molecular Genetics Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
  1. Correspondence to:
 Dr N J Prescott, Clinical and Molecular Genetics Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK;
 n.prescott{at}ich.ucl.ac.uk

    Recently, we reported a whole genome scan in sib pairs with non-syndromic cleft lip and palate (CLP), highlighting several regions as possible susceptibility loci, one of which is situated on 1p36.1 This region is of particular interest in CLP as it harbours the gene encoding MTHFR, an enzyme fundamental in the metabolism of the biologically active form of folic acid. Dietary folic acid deficiency has been considered as a candidate environmental factor in the aetiology of CLP in several studies. A study of CL/P cases born in the Czech Republic suggested that high dose (10 mg) folic acid supplements taken by pregnant mothers could decrease their chance of having a second affected CL/P child by 25-65%.2 Similar findings were reported in a case-control study in California for a much lower dose supplementation (<1 mg).3 Also, evidence provided by a Hungarian prospective cohort study and a study of the Hungarian Case-Control Surveillance of Congenital Anomalies data set showed that high dose folic acid supplementation during the critical stages of craniofacial development was the most effective at reducing the occurrence of oral clefting.4

    The MTHFR gene has a functional variant owing to the C677T substitution. This leads to a reduced activity of the enzyme after heating and homozygotes for this …