A team of researchers at the University of California San Diego School of Medicine conducted a study that sheds light on the causes of spina bifida, the most common structural disorder of the human nervous system. The study, led by Keng Ioi Vong, Ph.D., and Sangmoon Lee, M.D., Ph.D., in the lab of Joseph G. Gleeson, M.D., focused on identifying genetic links to spina bifida. They found a connection between spina bifida and a common chromosomal microdeletion in humans, which increases the risk of the condition by more than 10 times compared to the general population.
The research, published recently in the journal Science, also highlighted the potential role of folic acid as a preventive measure for spina bifida. Gleeson, the senior author of the study, explained that spina bifida affects one in every 3,000 newborns, with largely unknown causes. By establishing the Spina Bifida Sequencing Consortium in 2015, Gleeson’s lab collaborated with researchers globally to investigate a specific chromosomal deletion, 22q11.2del, in spina bifida patients. The study identified this deletion in several spina bifida patients, making it the most common genetic variation linked to the condition.
Further analysis by the researchers revealed that a single gene within the 22q11.2 deletion, CRKL, was likely responsible for causing spina bifida. Knocking out this gene in mice resulted in neural tube defects, including spina bifida, confirming its role in the condition. Additionally, the study explored the impact of folic acid supplementation on CRKL-mediated spina bifida, demonstrating that depriving Crkl mutant female mice of folic acid increased the severity of neural tube defects in their offspring. These findings suggest that folic acid could not only reduce the risk but also the severity of neural tube defects in offspring.
The researchers hope that their findings will deepen our understanding of the causes of neural tube defects, particularly those associated with common genetic variants such as the 22q11.2 deletion. They also anticipate that this research could contribute to healthier pregnancies, improved women’s health, and better outcomes for children. The study had several co-authors from the University of San Diego School of Medicine Department of Neurosciences and Rady Children’s Institute for Genomic Medicine, as well as other collaborative institutions. The work was supported by various grants, including from the Center for Inherited Disease Research, the National Institutes of Health, the Howard Hughes Medical Institute, and Rady’s Children Institute for Genomic Medicine, among others.
In conclusion, the study offers new insights into the genetic factors contributing to spina bifida, a common disorder of the nervous system. By identifying a link between a chromosomal microdeletion and spina bifida, as well as the potential role of folic acid in reducing the risk and severity of the condition, the researchers provide valuable information for future research and clinical practice. These findings have the potential to improve outcomes for individuals with spina bifida and contribute to advancements in prenatal care and women’s health.
