The Research On JAG1 Gene Mutation And Gene Expression In Congenital Heart Disease

ObjectiveCongenital heart disease(CHD) is a kind of congenital malformation caused by heart and major vessels ' abnormal development in fetal period.It is a kind of most common newborn defects,affects approximately 1%of infants,its incidence is estimated at close to ten times that level among abortus and stillbirths.CHD is the most common cause of noninfectious death in newborns.80%of CHD appears isolated CHD (other systems are normal).About 1/4-1/3 of CHD are conotruncal heart malformation. Studies have proved that CHD is a cardiac and vascular malfomation of multifactorial inheritance,which caused by genetic factors in embryonic phase and environmental factors,and the heritability is from 55%to 65%.JAG1 gene encodes a ligand of Notch receptor in the evolutionarily conserved Notch signaling pathway.It is very important in the embryonic development of homo-spapiens,it expresses in cardiovascular system mainly,the mutation rate is higher than other genes,now,there are more than 200 kinds of mutations have been found.The rearches of aboard presume that JAG1 gene is the virulence gene of Alagille syndrome(AGS,the major symptoms are:cholestasis, vertebral deformity,heart malformations,ocular defects and peculiar facial appearance), and the researches about JAG1 gene on CHD are limited in AGS,there are little identified reports are seen about JAG1 gene in isolated CHD.Through screening the mutations of JAG1 gene in isolated CHD and analyzing the expression levels of JAG1 gene in the cardiac muscular tissues,we want to approach the relationships between JAG1 gene and the pathogenesies in isolated CHD.MethodScreen the mutations of the coding sequences of JAG1 gene in 30 myocardium samples from the fetuses with isolated CHD by PCR-SSCP method;Using P-actin as internal control,we detected the differential expression between 30 myocardium samples from isolated CHD fetuses and 30 normal controls by reverse transcription polymerase chain reaction(RT-PCR).ResultsNo mutations were detected in exon2,4,5,6 of JAG1 gene in all samples by PCR-SSCP;The mRNA expression levels of JAG1 gene show descendent tendency in the samples of isolated CHD compared with normal controls.Conclusion1.Mutations in coding regions of exon2,4,5,6 of JAG1 gene may not cause human isolated congenital heart disease.2.The abnormality in transcription level of JAG1 gene may be a kind of mechanism causing human isolated congenital heart disease.