Whole Exome Sequencing For Pathogenic Genes In A Hypodontia And Tumor-prone Family

Objective Hypodontia is a common hereditary disease that occurs in the oral cavity.Many patients with missing tooth are often accompanied by a series of other systemic diseases,especially the occurrence of tumors.As more and more studies have found that congenital maxillofacial dysplasia and the occurrence of tumors share the same signal pathway.This study aims to provide a theoretical basis for the diagnosis,treatment and prevention of other hereditary diseases in the whole body through the preliminary study of the connection between hypodontia and systemic diseases.Content Hypodontia refers to the inability to develop and fail to form teeth in the process of tooth germ formation,or in the early stages of development of tooth germs.Many patients with congenital missing teeth are often accompanied by other systemic diseases or developmental abnormalities.Therefore,in this study,the clinical phenotype analysis and sequencing of whole genome exons in a family with hypodontia and multiple tumors were used to preliminarily discuss the intrinsic relationship between hypodontia and systemic diseases.Methods 1.Collect pedigrees with hypodontia and multiple tumors.Investigate family history and other data;conduct full-body examinations and oral specialist examinations on family members,analyze clinical data of families,and summarize clinical features.At the same time,draw the pedigree and do the genetic analysis;on the premise of all informed consent signed by the examinee,collect the venous peripheral blood of all family members who can get in touch.2.Whole exon sequencing: The degree of DNA degradation was analysised by agarose gel electrophoresis and whether there is RNA,protein contamination.The DNA samples with a content of 0.6ug or more were linearly amplified by PCR and subjected to library quality inspection.3.Full exon detection result description and analysis:Match the sequences to human reference genomes,detect variation information in samples,and make statistics and annotations on detected mutations.Based on the results of the mutation detection,the disease-associated harmful mutation sites or genes are screened by three analysis strategies based on the mutational harmfulness,the sample condition,and the gene function and phenotype.Results 1.After systematic examinations and dental specialties were performed on family members and the genetic characteristics of the family were analyzed.2.The probands and their mothers have 25 mutation sites in the DSPP gene,including 23 missense mutations in the exon region.3.There are six mutation sites in the gene AXIN-2 and there are two synonymous mutations located in the exon region.4.There are two mutation sites in gene ZNF609 related to megacolon disease.Both mutations are located in the exon region.One of them is a missense mutation with strong pathogenicity.5.Mutations in the AXIN-2 and ZNF609 genes might contribute to the susceptibility of tumors in this pedigree.Conclusion 1.The present study detected that the mutation of the AXIN-2 gene in probands and their mothers may be intrinsically linked to the hypodontia of the family and the development of megacolon.However,its pathogenic mechanism still needs further experiments.2.The tooth development related gene AXIN-2 shares WNT signaling pathway with the occurrence of colorectal tumors.The results of this study can further confirm the inherent relationship between hypodontia and tumors.3.Hypodontia is expected to become an extremely important risk indicator in future cancer research.