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
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."
In the current study, the researchers tested the DNA of 395 individuals
with a neural tube defect and 848 individuals who did not have a
neural tube defect. The researchers tested these people to see if
they had a variant of a gene known as 5,10-methylenetetrahydro-folate
reductase, involved in processing folate. The researchers conducted
the study in Ireland because that country has a high proportion
of individuals born with neural tube defects.
Human beings typically have two copies of a given gene, one inherited
from the father, and one from the mother. Previously, researchers
thought that an individual had to have two copies of the C677T variant
to be at increased risk of neural tube defects. However, the study
authors found that individuals having just one copy of C677T were
one and a half times more likely to have a neural tube defect than
were people who didn't have a copy of the variant gene. People with
two copies of C677T were two and a half times as likely to have
a neural tube defect than were people with two normal copies of
The researchers estimated that about 59 percent of the European
population and 53 percent of the North American population has either
one or two copies of the C677T variant.
In 1992, the U.S. Public Health Service recommended that all women
of childbearing age capable of becoming pregnant consume 400 micrograms
of folic acid, the synthetic form of the vitamin folate, from pills
or tablets. To reduce the number of neural tube defects, the U.S.
Food and Drug Administration required that folic acid be added to
the U.S. grain supply in 1998.
The addition of folic acid to grains has cut the amount of neural
tube defects in North America by about 50 percent, said the NICHD
author of the study, James Mills, M.D., chief of the NICHD's Pediatric
Epidemiology Section. Still, he added, on average, U.S. women of
childbearing age receive only about 200 micrograms a day of folic
acid from fortified grain. Women who don't eat grain products and
who don't take a vitamin preparation that contains folic acid may
be getting far less. In Ireland, where the study was conducted,
grains are not routinely fortified with folic acid.
[O]ur study provides new data underscoring the importance
of public health intervention programmes of folic acid supplementation
and food fortification targeted at all women of childbearing age
to prevent neural tube defects," the study authors wrote.
Dr. Mills explained that this gene could not be used as the basis
of a prenatal genetic test to diagnose neural tube defects. Although
having the gene increases the risk for neural tube defects, not
all individuals who have the gene are born with a neural tube defect.
The NICHD is part of the National Institutes of Health (NIH), the
biomedical research arm of the federal government. NIH is an agency
of the U.S. Department of Health and Human Services. The NICHD sponsors
research on development, before and after birth; maternal, child,
and family health; reproductive biology and population issues; and
medical rehabilitation. NICHD publications, as well as information
about the Institute, are available from the NICHD Web site, http://www.nichd.nih.gov,
or from the NICHD Information Resource Center, 1-800-370-2943; e-mail