• neural tube defects
• T gene
• MTHFR

• NTD, neural tube defects
• SBA, spina bifida aperta

Neural tube defects (NTDs) are likely to result from an interaction of several genes and environmental factors. A role for genetic factors is supported by the finding that first degree relatives of NTD patients have a significantly increased recurrence risk.^1,2 Since periconceptional folic acid supplementation of the maternal diet has been shown to have a preventive effect on occurrence and recurrence of the malformation, one contributing factor is believed to involve an altered folate metabolism.^3–5

Other potential candidate genes for human NTDs are offered by animal models. NTDs have been observed in a variety of mutant mice, spontaneously arisen or genetically engineered.^6,7 One of the candidate genes for human NTDs, the murine Brachyury gene (T gene), was recognised by virtue of its mutant phenotype. Mice that are homozygous for null mutations in Brachyury die in midgestation because of abnormalities in notochord and defects in other mesoderm derived structures. Heterozygous mice have short tails, notochord anomalies, and fusion of neural tube and gut in the caudal region.⁸ Studies of T gene expression pattern show that it is maintained in those cells that are absent in mutant mouse embryos, early stage mesoderm, tailbud, and notochord.^8,9

Brachyury encodes a DNA binding protein that functions as a transcription activator.¹⁰ After the cloning of the human homologue of Brachyury, human T,¹¹ Morrison et al¹² …