Neural Tube Defects from Even One Gene

Background: Neural tube defects (NTDs) are common birth defects of the brain and spinal cord that include anencephaly and spina bifida (meningomyelocele). Deficiency of the vitamin folic acid raises the risk of NTDs, as does mutation of a gene for an enzyme that processes folic acid. The mutation is called the C677T variant, or T for short.

Summary: People with two copies of the T mutation are two and a half times as likely to have a NTD as people with two copies of the normal gene. Now it has been found that people with just one copy of the T gene are also at increased risk for an NTD. They are one and a half times more likely to have a NTD than people with two copies of the normal gene.

Comments: NTDs provide a model of how the environment and genetics can interact to cause birth defects. The environmental factor is a lack of folic acid. It can be added to the diet. The gene has to do with the metabolism of folic acid.

It was thought that there had to be two mutant copies of the gene to raise the NTD risk. Now it is clear that even one copy of the mutant gene can raise the NTD risk. Even one gene can spell trouble.

Barbara K. Hecht, Ph.D.
Frederick Hecht, M.D.
Medical Editors, MedicineNet.com

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U.S., Irish Researchers Identify Important Clue to Genetic Basis for Neural Tube Defects

A team of U.S. and Irish researchers has come one step closer to understanding why a high proportion of the population is genetically at risk for neural tube defects, according to a genetic study by researchers in Ireland and at two of the National Institutes of Health, the National Institute of Child Health and Human Development, and the National Human Genome Research Institute.

Specifically, the researchers learned that having only one copy of a variant gene is enough to increase the chances of being born with a neural tube defect. Previously, researchers believed that two copies of the gene were needed to increase someone's risk of being born with a neural tube defect.

The finding underscores the need for all women of childbearing age to follow the current recommendation to take 400 micrograms of the vitamin folic acid each day.

The study appears on the Web site of the British Medical Journal, at http://bmj.com and will appear in the print edition of the journal at a later date.

Neural tube defects are a class of birth defects affecting the brain and spinal cord. In one type, spina bifida, a piece of the spinal cord protrudes from the spinal column, causing paralysis below the protrusion. In anencephaly, a fatal neural tube defect, the brain and skull are grossly underdeveloped.

The study was funded by the NICHD and the Health Research Board of Ireland.

Although the gene increases the chances for a neural tube defect, not all people who have the gene will develop a neural tube defect. Neural tube defects occur in about 7 of every 10,000 pregnancies. Women can reduce their chances of giving birth to a child with a neural tube defect if they take a tablet containing 400 micrograms of folic acid each day in the weeks before they become pregnant and throughout their early pregnancies. All women of childbearing age are advised to take 400 micrograms of folic acid each day, regardless of whether or not they are planning to become pregnant, as the majority of pregnancies in the United States are unplanned.

"Although we've made great progress in reducing the number of neural tube defects in the United States, not all women are receiving the recommended amount of folic acid," said Duane Alexander, M.D., Director of the NICHD. "This study underscores the need for all women of childbearing age to make sure they're taking 400 micrograms of folic acid a day."