Novel mutations identified in patients with tooth agenesis by whole‐exome sequencing

Abstract

Objectives

To identify potentially pathogenic mutations for tooth agenesis by whole‐exome sequencing.

Subjects and Methods

Ten Chinese families including 5 families with ectodermal dysplasia (syndromic tooth agenesis) and 5 families with selective tooth agenesis were included. Whole‐exome sequencing was performing using genomic DNA. Potentially pathogenic mutations were identified after data filtering and screening. The pathogenicity of novel variants were investigated by segregation analysis, in silico analysis and functional studies.

Results

One novel mutation (c.441_442insACTCT) and three reported mutations (c.252delT, c.463C>T, and c.1013C>T) in EDA were identified in families with ectodermal dysplasia. The novel EDA mutation was co‐segregated with phenotype. A functional study revealed that NF‐κB activation was compromised by the identified mutations. The secretion of active EDA was also compromised detecting by western blotting. Novel Wnt10A mutations (c.521T>C and c.653T>G) and EVC2 mutation (c.1472C>T) were identified in families with selective tooth agenesis. The Wnt10A c.521T>C mutation and the EVC2 c.1472C>T mutation were considered as pathogenic for affecting highly conserved amino acids, co‐segregated with phenotype and predicted to be disease‐causing by SIFT and PolyPhen2. Moreover, several reported mutations in PAX9, Wnt10A and FGFR3 were also detected.

Conclusions

Our study expanded our knowledge on tooth agenesis spectrum by identifying novel variants.

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