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First Genetic Screen Reveals Possible Gene Loci for Neural Tube Defects


For release: Monday, May 9, 2005

Dozens of investigators studying nearly 300 individuals from 44 families nationwide have narrowed down the hunt for genes that may cause such birth defects as spina bifida and anencephaly.

Results of the first full genetic analysis of families having two or more related members with neural tube defects (NTDs) identify several possible locations for genes causing the disorders, particularly on chromosomes 7 and 10. The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS). Findings appear in the April 14, 2005, online edition of the Journal of Medical Genetics.

"Inherited and environmental factors such as exposure to certain medicines, chemicals, or diet are believed to cause NTDs," said Katrina Gwinn-Hardy, M.D., an NINDS program director for neurogenetics. "The information produced by this study will allow gene discovery to proceed even faster and may lead to a better understanding of causes and potential therapeutic and preventative strategies for these disorders."

NINDS grantee Marcy Speer, Ph.D., Duke University Medical Center, and colleagues from across the country screened the genetic make-up of 44 families having at least two related individuals with NTDs. A total of 292 family members were included in the study. DNA samples taken from whole blood were screened for genetic markers on various chromosomes to identify any regions that might harbor defective genes.

Results from the 89 individuals with an NTD identified intervals on chromosomes 7 and 10 as having the highest scores. A review of public databases revealed three biologically plausible candidate genes on chromosome 10 that map closely to the identified region. A single family pedigree contributed significantly to the high score on chromosome 7. Other regions of interest were found on chromosomes 11, 15, and 21. Results of this screening may prioritize candidate gene assessment in future studies of NTDs.

Of the 23 pairs of chromosomes in the human genome, chromosome 7 is one of the largest, containing about 5 percent of our DNA. Chromosome 10 represents between 4 and 4.5 percent of the total DNA in cells.

"We’ve narrowed down the genome from something huge to initial regions of interest for NTD candidate genes," said Dr. Speer.

She called the study a "a hugely collaborative success" that involved hundreds of patients and family members, as well as a large number of investigators in the NTD Collaborative Group — a research consortium of 13 universities and hospitals across the country. Large studies of multiplex (involving at least two related family members) NTD family pedigrees are difficult to conduct because of the increased risk of death associated with the disorders and termination of affected pregnancies detected in prenatal exams.

NTDs occur when the narrow sheath that forms the brain and spinal cord remains open. The sheath usually closes by the 28th day of pregnancy. Failure to close properly can result in disorders including spina bifida (in which some of the spinal cord protrudes from the spinal canal, causing paralysis below the site) and anencephaly (a fatal defect involving a severely underdeveloped brain and spinal cord). Inherited and environmental factors such as exposure to certain medicines, chemicals, or diet are believed to cause NTDs.

Studies have shown that women who take 40 micrograms of vitamin B9 (folic acid) before pregnancy and during the first trimester can reduce the incidence of NTDs by 50 to 70 percent. It is still possible, however, for a mother who takes the recommended amount of folic acid during the recommended time period to have a child with the defect. Why this happens is still unclear.

Women who have had a baby with a neural tube defect have a 2 to 5 percent chance of having another NTD affected pregnancy, a 50-fold increase over the general population. The risk is increased to 4 percent in children of a person with an NTD.

The NINDS is a component of the National Institutes of Health within the Department of Health and Human Services and is the nation’s primary supporter of biomedical research on the brain and nervous system.

-By Paul Girolami

Last Modified January 31, 2007