Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida

Lancet. 1995 Oct 21;346(8982):1070-1. doi: 10.1016/s0140-6736(95)91743-8.


Periconceptional folate supplementation reduces the risk of neural-tube defects. We studied the frequency of the 677C-->T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene in 55 patients with spina bifida and parents of such patients (70 mothers, 60 fathers). 5% of 207 controls were homozygous for the 677C-->T mutation compared with 16% of mothers, 10% of fathers, and 13% of patients. The mutation was associated with decreased MTHFR activity, low plasma folate, and high plasma homocysteine and red-cell folate concentrations. The 677C-->T mutation should be regarded as a genetic risk factor for spina bifida.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Folic Acid / blood
  • Gene Frequency
  • Homocysteine / blood
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Point Mutation*
  • Risk Factors
  • Spinal Dysraphism / genetics*


  • Homocysteine
  • Folic Acid
  • Oxidoreductases Acting on CH-NH Group Donors