Professor Kim Sang-woo of Yonsei University College of Medicine identified the genetic causes of congenital spina bifida in collaboration with researchers from the University of California, marking the first discovery in the world. The research results were published in the international journal Nature on the 27th.
Spina bifida is a congenital deformity that occurs when the neural tube, which forms the central nervous system during fetal development, does not close completely. In severe cases, a spinal meningocele may occur, leading to mobility impairments and sensory abnormalities. Meningocele refers to a condition in which the membranes surrounding the brain and spinal cord are not formed, leaving nervous tissue exposed.
The research team focused on the possibility that the genetic cause of spina bifida manifests only in children and not in their parents, highlighting de novo mutations. At the same time, the University of California researchers were conducting genetic analysis on 851 patients with spina bifida and 2,451 family members worldwide to find the causes of the disease.
The team analyzed DNA obtained from patients with spina bifida and their families using a technique called whole-exome sequencing (WES), confirming the presence of de novo mutations after three years. These mutated genes are primarily responsible for functions related to maintaining cell structure, neuronal signal transmission, and chromatin modification. The research team also confirmed through animal experiments the impact of these gene mutations on the neural tube defect process.
Despite being a serious congenital deformity, the incidence of spina bifida is as high as 1 in every 3,000 newborns. Professor Kim noted, "It can be considered a relatively common disease among rare diseases, and patients with spina bifida must live with developmental disabilities or urinary disorders throughout their lives, leading to high social and economic expenses."
The causes of spina bifida can be broadly categorized into genetic and environmental factors. Among these, environmental causes are relatively well understood. The biggest environmental factor is a deficiency in vitamin B-9, commonly known as folate. One reason pregnant women are encouraged to consume folate is to avoid spina bifida. Many countries have confirmed that folate intake lowers the incidence of spina bifida.
On the other hand, much remains unknown about the genetic causes. Unlike common genetic disorders, identifying the key genes associated with spina bifida has long posed a challenge. While some genes have been identified through animal experiments, the complex nature of the disorder, which is influenced by environmental factors, has made it difficult to determine definitive genetic causes.
Professor Kim said, "The causative genes for spinal meningocele revealed through this study could also be used in the future for developing disease prediction models," adding, "Not only for congenital neurological disorders like spinal meningocele, but also for other complex diseases like zipper syndrome, identifying genetic causes has been very challenging, and applying this research method could unveil new facts."
References
Nature (2025), DOI: https://doi.org/10.1038/s41586-025-08676-x