208 Bone Morphogenetic Proteins Genes and Neural Tube Defects

Abstract

Neural tube defects (NTD) are among the most common and severe congenital defects. The genetic background of a failure in the neural tube closure, which is the cause of NTD remains unknown. Among potential candidate genes which may contribute to the etiology of these defects the family of BMP (bone morphogenetic proteins) genes is considered. The aim of the study was to analyze the possible causative role of mutations of the BMP-2, BMP-4 and BMP-9 genes in the development of NTD. Methods: Genomic sequences of the BMP-2, BMP-4 and BMP-9 genes were amplified by means of PCR technique and subsequently screened for mutations (denaturating high-performance liquid chromatography - DHPLC) in children with NTD. DNA fragments showing an abnormal DHPLC pattern were further directly sequenced to confirm the presence of the mutation. Subsequently, the frequency of the variant was analyzed and compared between the tested group of patients and the control group. Results: 112 children with NTD were enrolled to the study. The control group consisted of 110 healthy children. No mutations were detected within the BMP-2 gene and 1 silent polymorphism (C>T transition in the 142nd codon of the 2nd exon of the gene, no change in protein sequence) was found in the BMP-9 gene. In the BMP-4 gene, the polymorphism was found (538T>C transition with subsequent change of the protein sequence: 147Valine>Alanine). The frequency of 538CC homozygotes in the NTD group was higher (34.8%) than in the controls (26.4%), but the difference did not reach statistical significance (odds ratio 1.49; 95% confidence interval 0.84–2.63; p value in chi-square test 0.17). Conclusion: No mutations within the BMP-2, BMP-4 and BMP-9 genes were detected. The role of these genes in the development of NTD remains uncertain. The study was sponsored by a grant from State Committee for Scientific Research (No. 3P05E13823).