When the spine or spinal cord do not form properly during human development, a disorder called spina bifida, or meningomyelocele arises. People born with this condition can have very different challenges; some may have intellectual disability while others have neurological issues, for example. The exact causes of spina bifida are unclear, but it is one of a group of disorders known as neural tube defects. Scientists have now learned more about how spina bifida develops. These findings, which have been reported in Nature, could also help scientists find better treatment options.
Spina bifida is can be diagnosed in a few ways, but it is often seen during a prenatal ultrasound. Genetics, environmental factors, and dietary factors can all play a role in the development of the condition. Folate deficiency is a known risk factor, and doctors recommend that pregnant women or those preparing for pregnancy should take a folic acid supplement. The physiological link between folic and and spina bifida is still unclear, however.
This latest study has suggested that so-called de novo genetic mutations, which arise in the fetus but are not carried by either parent, may be one cause of spina bifida. In this work, the researchers analyzed DNA from many parent-child groups, including hundreds of children with spina bifida.
This analysis indicated that de novo mutations are a significant contributor to spina bifida risk. About one-quarter of patients carry novel mutations that are related to the disorder (and which are not carried by their parents).
The work also revealed molecular pathways that are relevant to the disease. The genetic mutations that were identified seem to affect how embryonic cells are connected.
"Our research identifies specific steps in embryogenesis that contribute to spina bifida," said senior study author Dr. Joseph Gleeson, a professor at Rady Children's Institute for Genomic Medicine and the University of California, San Diego. "This is a major step forward in understanding why this condition occurs and how we might one day prevent it."
"Our results identifying genetic risk factors can now be used to develop new screening tools to achieve a more accurate and earlier diagnosis, and possibly predict the degree of disability," said first study author Dr. Yoo-Jin Ha, of UC San Diego and Yonsei University College of Medicine in South Korea.
The investigators want to create better methods to detect mutations that may increase spina bifida risk to improve diagnostics. They also want to learn more about the potential for gene therapy, novel drugs, or dietary interventions that may prevent the disease.
Sources: Rady Children's Institute for Genomic Medicine, Nature
