Mutation Analysis Of FOXC2 Gene In Congenital Developmental Defect

Mutation analysis of FOXC2 gene in congenital developmental defectIn embryonic development, by environmental, genetic and other factors, the fetus development of the appearance, structure and physiological function were affected, fetal abortion, stillbirth or birth defects often exist,it's a heavy economic and psychological burden to the family and society. Congenital developmental defects were large proportion mortality in the fetal and neonatal. it's a serious impact on quality of health diathesis. Find the exact cause of congenital defects, and further reveal its pathogenesis, it's great significance for prenatal prevention, diagnosis and intervention, and improve the quality of births.Human forkhead box c2 (FOXC2),a member of the winged helix transcription factors family with DNA-binding domains, was evolutionarily highly conserved.The positiong was 16q22-16q24, it only Contained a single coding exon, no intron, the length of cDNA was 1506bp. The protein encoded 494 amino acid residues. Animal experiments have proved, Foxc2 gene in embryonic development played an important role. in gene knockout mice showed abnormalities in cardiovascular, cartilage, kidney, aortic arch and the eyes and other parts of the stroma.Human FOXC2 have been cloned, the human FOXC2 gene and the gene in mice Foxc2 had more than 95% homology.The first relevance of the human FOXC2 gene and clinical disease was confirmed in a hereditary disease-lymphedema -distichiasis syndrome.LD syndrome was a rare autosomal dominant genetic disease. The clinical characteristics were lower limb edema and double eyelashes, and the individual merge varicose veins, congenital heart disease and ptosis.The genetic analysis of LD family found that the FOXC2 gene mutations and LD syndrome were closely related. In animal experiments,it has found that Foxc2 was related with lymphangiogenesis, the development of axial skeleton, cardiovascular system and urinary system.However, in human embryonic development, the gene expression of molecular biology and functional status is not clear, So we did the the research,we want to know the relationship with FOXC2's role in embryogenesis and congenital developmental defects. Partâ… Autopsy type analysis of congenital developmental defects fetalObjective: Analysis of congenital developmental defects in Changchun, and provide the theoretical basis on the prevention of point defects.Methods: Collected 73 cases of developmental defects fetus that were abortion and induced in Obstetrics and Gynecology department of several hospital in Changchun. We recorded obvious malformations and analysis of abnormal organs. Results: In the 73 cases of congenital abnormalities fetus, male were 41 cases, female were 32 cases. Since a fetus could occur malformations or defects in several tissues and organs, 93 cases of malformations were found in different organ and tissue,they caused 32 cases intrauterine fetal death. The largest number of malformations were neural tube defects, 47 cases. accounting for 64.3%(47/73)of fetal abnormalities,the composition ratio of total malformations was 50.5%(47/93).The number of cardiovascular abnormalities were 19, accounting for 26% (19/73)of fetal abnormalities,the composition ratio of total malformations was 20.4% (19/93). Stillbirth of cardiovascular abnormalities were 15 cases, cardiovascular abnormalities fetal death rate was 78.9% (15/19), accounting for the total number of abnormal stillbirth 46.9% (15/32).Conclusion: In 73 cases of congenital developmental defects fetus, the proportion of male was more than female. Neural tube defects was the most important congenital developmental defects in Changchun area. Cardiovascular abnormalities in this region was also the major congenital developmental defects,it was the main reason caused intrauterine fetal death.We found lymphedema fetus similar to adult LD syndrome.Partâ…¡FOXC2's a important transcription factor in the human embryonic development of many organsObjective: To know if FOXC2 was involved in the development of human embryos. Methods:We analyzed FOXC2's role in the human embryonic development by Immunohistochemical methods.Results: In the human embryo,FOXC2 first occurred in the head mesenchyme. Then In the costal rib cartilage primordial germinal center found strong expression of FOXC2 protein in the nucleus. We could found FOXC2 expression in the the great vessels of heart, whole layer of aortic,the ventricular endocardium and the ventricular outer wall. Embryonic kidney medulla also had FOXC2 expression. Conclusion: FOXC2 gene was the indispensable transcription factor in the process of development of central axial skeleton; FOXC2 played an important biological effect in the process of development of human embryonic cardiovascular system; The development of human embryonic kidney also need FOXC2 participation.Partâ…¢The analysis of risk factors for fetal congenital developmental defects and FOXC2 gene polymorphismObjective: To understand the relationship of risk factors with congenital developmental defects ,and FOXC2 gene mutation with congenital developmental defects.Methods: The risk factors were investigated, registed and analysis of 73 cases congenital developmental defects fetus.Extract their genomic DNA, amplified FOXC2 cDNA fragment by PCR,and inspect sequencing,then analysis the genetic polymorphism. Results: The occurrence of congenital defects fetus were closely related with parents' bad habits, family heredity history of developmental defects,parents' special work history, history of exposure to specific chemical agents, no progestation examination and without supply folic acid and vitamins in early pregnancy. 68 cases of target DNA fragment were successful sequencing,there were 20 mutations, which caused 15 amino acid changes in sites. The 15 effected mutations concentrated in 12 cases (including the neural tube defects, cardiovascular abnormalities, fetal lymphedema and polycystic kidney fetus), FOXC2 gene mutation rate was 17.6% (12/68). Conclusion: Gene mutation analysis found FOXC2 multiple mutation spots in embryogenesis congenital defects with neural tube defects, cardiovascular dysplasia,lymphedema and polycystic kidney.The embryonic period lymphedema fetus showed similar high FOXC2 mutation rate to adult LD syndrome.The FOXC2 mutations of embryonic developmental defectfetus caused change of encoding amino acids,so FOXC2 gene mutations had close relationship.with birth defects.Partâ…£The analysis of risk factors for congenital heart disease and FOXC2 gene polymorphismObjects: To understand the relationship of risk factors with congenital heart disease,and FOXC2 gene mutation with congenital heart disease.Methods: Collected 34 children's myocardium with congenital heart disease in cardiac surgery of the First Hospital of Jilin University.The risk factors were investigated, registed and analysis of 34 cases CHD patients.Extract their genomic DNA, amplified FOXC2 cDNA fragment by PCR,and inspect sequencing,then analysis the genetic polymorphism. Results: The occurrence of CHD were closely related with parents' bad habits(smoking and drinking), history of exposure to specific chemical agents, family heredity history of developmental defects, drug administration and flu in early pregnancy. 29 cases of target DNA fragment were successful sequencing,there were 9 mutations, which caused amino acid changes in sites. The 9 effected mutations concentrated in 7 cases, FOXC2 gene mutation rate was 24.1%(7/29).Conclusion: Variety of factors during pregnancy can cause the increased incidence of CHD.FOXC2 gene mutations had close relationship.with CHD. The FOXC2 mutations of CHD patients caused change of encoding amino acids,so FOXC2 gene mutations had close relationship.with CHD.The site of FOXC2 gene in 216bp, 255bp and 505bp mutation common occurred in CHD patients and cardiac defect fetus,it proved that the three mutation sites were congenital heart disease mutation hot spots.