Recent Progress in
NTD Research at Duke
University Medical Center
By: Liz Melvin, MS, COC, Study Coordinator and Debbie Siegel, Patient Coordinator Duke
University Medical Center
Duke University Medical Center CDUMC) has an ongoing, long-term research study aimed at
discovering the genetic and environmental factors that cause neural tube defects (NTD’s). This
study is a highly collaborative effort involving 12 myelodysplasia clinics throughout the country.
We are searching for families in which one or more family members has spina bifida or other
type of NTD, a thoracic level NTD, or lipo(myelo)meningocele. Approximately 800 families
from the US and Canada are in the study.
Along with actively enrolling new families, the Duke researchers are busy in the laboratory.
NTDs are considered a complex disorder because they are caused by a combination of genetic
and environmental factors. There are two major laboratory analyses that scientists use to find
genes contributing to complex disorders. One strategy, called a genome scan, systematically
searches each chromosome, looking for areas potentially harbouring the genes related to NTDs.
Our laboratory has already begun the second strategy, which looks at candidate genes. Candidate
genes are genes in which the location and function is known- Candidate genes for NTDs are
often related to neural tube development or how our body uses folic acid. Three different types
of candidate genes are useful for studying NTDs. First, because of the known benefit of folic
acid on neural tube closure, any gene involved in the folic add metabolic pathway is a potential
candidate. In particular, the gene coding for methylenetetranydrofolate reductase (MTHFR) has
been a hot topic of recent research. Particular changes in this gene have been reported to
contribute to NTDs in some families in Europe; however, our laboratory does not confirm these
results in North American Caucasians.
Further work on MTHFR includes studying if an interaction exists between a mother's MTHFR
genes and the fetus's MTHFR genes. Our laboratory and others are also studying if an interaction
exists between MTH FR and another folic add gene called cystathionine beta-synthase.
Preliminary results suggest evidence for an interaction between these two genes. However,
further study is needed. MTHFR continues to be actively studied by many researchers and is
only one piece of the complicated puzzle.
Second, there are some genes known to cause NTDs in mice and other animals. Researchers
know a lot more about mouse genes than human genes. Despite our differences from other
animals, we share many of the same genes. There are over 40 genes that cause NTDs in mice.
Our laboratory is actively trying to study each one to see if these genes are important in causing
human NTDs. So far, none of these genes is strongly related to human NTDs. Lastly, genes may
be identified in individuals who have both a neural tube defect and a chromosome change.
Sometimes, a piece of one chromosome breaks off and attaches to another chromosome. If this
break occurs in the middle of a gene important in neural tube development, then the gene may
not work properly and a NTD may develop. Our laboratory plans to study these families.
It is only through the development of new laboratory and computer technology in the last 10
years that studying complex disorders like NTDs is even possible. This research is very exciting.
With the help of more interested families, this research will continue at a faster pace. We are
actively seeking additional families who would like to participate in the study. Participation is
free and does not require travel to DUMC. Participation involves a telephone interview, review
of medical records of the family member with a NTD, and collection of blood samples from
some family members. Please contact us at (919) 684-4787 if you are interested in participating.