Mutation Analysis Of FOXC2 Gene In Congenital Defect Fetus

Congenital fetus malformation also calls the embryo's birth defect ,which possesses fairly protortion in the mortality of fetus and newborn. Its morbidit is about 15‰abroad and about 13.7‰in China. It is a disease which seriously affects the health of the de novo population. Human forkhead box c2 (FOXC2),a member of the winged helix transcription factors family with DNA-binding domains, is evolutionarily highly conserved. Recently,a series of animal models suggest that lacking FOXC2 gene mice embryon display the development defects of cardiovascular system and axial skeleton. In addition, FOXC2 gene mutation is related to Lymphoedema-Distichiasis syndrome (LD).Our research is to detect this gene mutations in the human congenital fetus malformation. We'd like to reveal the relationship between this gene and the human congenital fetus malformation.We collected 66 cases suffered from congenital fetus malformations which underwent pathoanatomy examination, and the occurrence profile of various congenital developmental defects was described. These fetuses were induced labor and abortion clinically. Genomic DNA was extracted from these developmental anomaly fetus tissues and the whole coding sequence of FOXC2 was amplified by polymerase chain reaction( PCR). From this ,it could be proved that these genomic DNA were available. To discover if these available genomic DNA had FOXC2 gene mutation, these DNA went through the whole coding sequence determination of FOXC2 gene.Finally, we try to interpret the relationship of the FOXC2 and congenital fetus malformation. The results showed that in 66 cases suffered from congenital developmental malformations, the cases of cardiovascular anomaly was the most, which was 25.8% of all developmental defects and 53.6% of the account of fetal deaths. There were 15 anencephalus. The constituent ratio of Hydrocephalus, spina bifida and meningocele were equal and over 10%, respectively. Cleft palate, lymphedema and the kidney anomaly took a constituent ratio at 7.6%, respectively. According to system categorization, the proportion of the neural tube abnormity was the most, the next was malformation of cardiovascular system ,the last was the axial skeleton defects. In addition, the developmental anomaly of lymphatic system with cardiovascular abnormality also possessed higher proportion. However, the most important cause of stillborn was cardiovascular abnormality.Genomic DNA was extracted through the use of a DNA isolation. By sequencing the genomic DNA directly, and comparing the gene order which is logging in the NCBI GenBank with it, we found that the polymorphism resided in the 762th basic group(gene order 1958) of FOXC2 gene coding region. That's to say the third basithymidylic acid T of the 254th genetic codon inverted to the cytidylic acid C. Genetic codon GGT was changed into GGC. Whether genetic codon GGT or genetic codon GGC ,their corresponding amino acid residue was glycine(Gly). This amino acid residue was not in the forkhead domain of FOXC2 protein, but in the C-end of the forkhead domain, which was away from the 62 amino acids of forkhead domain. However, the mutation did not change the primary, secondary and tertiary structure, because this mutation did not cause the change of the amino acids.Our results show that although the neural tube abnormity constructs the most part of congenital fetus malformations, the cardiovascular system is the most important reason leading to fetal death and dead birth.There is polymorphism in FOXC2 gene coding region .This regional mutation is not in the alreadly reported single nucleotide polymophism(SNP). From this ,we can see that there are SNPs of FOXC2 gene in the different race of people possibly.However,We need a deep research from more large sample.