Trends Genet. 2026 Mar 18:S0168-9525(26)00030-2. doi: 10.1016/j.tig.2026.01.011. Online ahead of print.
ABSTRACT
Spina bifida is a clinically and etiologically heterogeneous group of neural tube defects (NTDs) that includes meningomyelocele. While folic acid (FA) supplementation has reduced the incidence by 30-50%, genetic contributors remain only partially understood. New trio sequencing technology has identified de novo mutations (DNMs) in 20-25% of patients. Two recent large-scale genomic studies identified DNMs in 187 candidate genes and a recurrent 22q11.2 deletion as risk factors. Partial penetrance and variable expressivity are frequent, suggesting that risk is dependent upon FA and other modifiers. The Spina Bifida Sequencing Consortium supports large-scale data sharing for multidisciplinary approaches, emphasizing high-confidence NTD genes and moving the results toward clinical testing.
PMID:41850968 | DOI:10.1016/j.tig.2026.01.011