Standardized Birth Defects Encyclopedia Construction Predicts New Mechanism For Birth Defects

There exist a wide variety of birth defects and most of them are rare diseases,which makes large number of children can hardly get effective diagnosis and treatment owing to their unknown pathogenesis.Although multiple mature disease databases have been established by different health constitutes throughout the world,no comprehensive knowledge systems have been built on research related to birth defect.The above circumstances have brought difficulties in the implementation of precision medicine.Based on these,this paper integrated a total of 12,687 standardized birth defects and added the annotation of their clinical information.What's more,this program also extracted 5,098 standardized cases for 80 rare birth defects from PubMed based on a set of strict quality-control criteria.As a result,the eBiDD(http://119.3.41.228:8080/Bi rthDefect/),a standardized knowledge base for birth defect,has been built up.Moreover,in order to verify the reliability of the role of eBiDD in advancing molecular mechanism research,this paper also conducted relevant analysis on two rare birth defects-Osteogenesis Imperfecta(OI)and Berardinelli-Seip Congenital Lipodystrophy(BSCL).First,this paper evaluated the genotype-phenotype association based on the clinical cases from eBiDD to explore their potential pathogenic mechanisms.Next,we combined traditional disease network analysis,pathway enrichment analysis and phenotype similarity analysis to predict potential pathogenic factors for them.Finally,we also conducted literature surveys and adopted mouse models to confirm the reliability of the prediction results.As a result,we totally identified six candidate pathogenic variations(COL1A1: c.3290G>A(p.Gly1097Asp),c.3289G>C(p.Gly1097Arg),c.3289G>A(p.Gly1097Ser),c.3281G>A(p.Gly1094Asp);COL1A2: c.2332G>T(p.Gly778Cys),c.2341G>T(p.Gly781Cys))and three potential pathogenic genes(ADAMTS2,COL5A2,COL8A1)for OI.We also identified two potential pathogenic genes(CAV3,EBP)for BSCL,and the genotype-phenotype association analysis result reveals that in different subtypes of BSCL,some phenotypes exist differential distributions between females and males.The results of this program provide new insights into the study of complex mechanisms of other birth defects and the implementation of precise treatment.