Formate prevents most folic acid-resistant neural tube defects
The human connection
To determine whether the findings in mice could be connected to human neural tube defects, the researchers conducted genomic studies in a cohort of patients with this condition and found one individual carrying a non-functional variant of the SLC25A32 gene.
“We know that the patient has a neural tube defect, but we would need further studies to determine how involved the SLC25A32 gene is in the condition,” Finnell said. “Neural tube defects can be caused by variants in over 300 genes in the mouse, so we anticipate that many genes also are likely to be involved in the human condition.”
“I am most excited about the connection we have made between the mouse model and the human condition through the SLC25A32 gene,” Lei said. “We now have a novel mouse model of human neural tube defects in which we can study the complex interactions between genetics and the environment that lead to this condition, and explore strategies to prevent the defects from happening.”
“My lab is all about preventing preventable birth defects,” Finnell said. “Even though we do fortify foods with folic acid, there are still babies born with neural tube defects. Folic acid has been a major public health advance, but the problem has not disappeared. We cannot lose sight of the fact that babies can still be born with neural tube defects even when the mothers take folic acid supplements.”
Other contributors to this work include Jimi Kim, Jin Guo, Sung-Eun Kim, Bogdan Wlodarczyk, Robert Cabrera, Ying Linda Lin, Torbjorn K. Nilsson, Ting Zhang, Aiguo Ren, Linlin Wang, Zhengwei Yuan, Yufang Zheng, and Hongyan Wang. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine; The University of Texas at Austin Dell Medical School; Capital Institute of Pediatrics, Beijing; Umea University, Umea; Peking University, Beijing; China Medical University, Shenyang and Fudan University, Shanghai.
Financial support for this project was provided by grants from NIH (HD081216, HD083809, and HD067244), CAMS Initiative for Innovative Medicine (2016-I2M-1-008), the Program of China (2013CB945400), the National Key Research and Development Program, Ministry of Science and Technology, P.R. China (2016YFC1000501) and the National Natural Science Foundation of China (81472987).