Mutation Analysis For Patients With Ectodermal Dysplasia Or Selective Tooth Agenesis

Purpose: This study aimed to find the potentially pathogenic mutations in patients with ectodermal dysplasia（ED）or selective tooth agenesis（STA）and investigate the pathogenicity of the mutations by functional studies.Materials and Methods: Peripheral venous blood was taken from the patients with ED or STA and genomic DNA was then extracted from the blood samples.Whole-exome sequencing（WES）was performing using the DNA samples.Sequencing data was then filtered and screened to identify the potentially pathogenic mutations.Some functional studies were also performed for the pathogenicity verification of the identified variants.Results: WES was performed using genomic DNA from five ED patients and one STA patient.Quality analysis of WES data showed that the sequencing data was qualified for further analysis.After filtering and screening of the WES data,four EDA mutations were identified in ED patients,including two frameshift mutations（c.252 delT and c.441₄42insACTCT）and two missense mutations（c.463C>T and c.1013C>T）.The two frameshift mutations which would destroy all the three important domains of EDA protein were found to influence the secretion of active EDA and further decrease the activation of NF-κB signal pathway.The EDA c.463C>T mutation was found to compromise the secretion of soluble EDA and influence the NF-κB pathway activation.EDA c.1013C>T could also compromise the NF-κB pathway activation.The WNT10 B c.1099C>T mutation was detected in the STA patient.WNT10 B belongs to Wnt superfamily and could active the Wnt/β-catenin pathway.We found the WNT10 B mutation did not influence the protein expression,but compromised the activation of Wnt/β-catenin pathway.Conclusion: Potentially pathogenic mutations were identified in ED or STA patients and the pathogenicity of these mutations were verified by functional studies.This study provided basis for the early diagnosis and genetic counseling of ED or STA patients.