Congenital Heart Disease And Cataract Genetics Research

Objective:Congenital heart defectisthe most common congenital malformations type in children,seriouslyendangeringchildren’s health and life,andcosting large amounts oflimitedpublicmedicalresources.Itis important for early detection,diagnosis and treatment bylearningthe mechanismof CHD and mastering thepathogenesis of heart disease,which is significant inreducingmortality and fertilityinpatientswithCongenital heart defect.The first partofthisthesismainlyfocuses ontheetiology and pathogenesisof CHDbased on themolecular geneticstechniques.Cataract is a clouding that develops partor all in the crystalline lens,thecataractisa major causeofblindness.In our country,the congenital cataract has been reported in 0.04%of those newborn,andhas the incidence of0.01-0.06%in Europe and the United States.Aboutl 8 miillionpeople’s blindness is due tocataract,and themajorityofpatients are inAfrica and Asia.We analyzed the sequences in patients with congenital cataract by direct sequencing,and analyzed the relationship between genetic vartions and the pathogensis of cataract,which may help investigate the biology of lens differentiation,development and mature,and fundamentally analyze therelation of genetype and phenotype,mutant and character of protein,and mutant and pathogensis of cataract.Methods:The HEY2is associated with the development of cardiac,and the CRYAA,CRYAB,CRYBA1,CRYBB2,CRYGC,CRYGD,CRYGS,GJA3,GJA8are associated with the congenital cataract,based on the function of those genes.Those genes were being investigated by direct sequencing of coding region in CHD and cataract patients.The discovered variations were performed function predictions using applied bio informatics.The mutant type of CRYGC was cloned and expressed in human lens epithelial cell.Results and Conclusion:In the study of CHD,we did not reveal any diagnostic alterations in the coding regions by direct sequencing in HEY2.However,this work expands our knowledge of the cause of CHD in a new perspective.In the study of cataract,we detected 19 variations in four families,including 11 variations in CRYBB2 and 3 in CRYGD,and each of CRYGC,GJA3,CRYAA,CRYAB and CRYBA1 had one variation.In the family Cat-02,we detected a nonsense variation,rs74315489,and in the family Cat-01,we found a missense variation ss325992558（NP₀66269p.G129C）.On the other hand,we detected four synonymous variations,including ss290489935（NP₀08822:p.Arg95=）,ss290489940（NP₀08822p.Tyrl7=）,ss290489938（NP₀05199.2p.Gly152=）and NP₀00487.1 p.P 157=.The synonymous variations,whichmayaffect the transcription factor binding efficiency,were performed codon bias analysis.These studies help us understand the congenital cataract,and explain the pathological mechanisms of cataract based on the molecular genetics.