Journal
ORAL DISEASES
Volume 25, Issue 2, Pages 523-534Publisher
WILEY
DOI: 10.1111/odi.13002
Keywords
craniofacial anomalies; ectodermal dysplasia; NF-kappa B pathway; oligodontia; tooth development
Categories
Funding
- Combined Engineering and Medical Project of Shanghai Jiao Tong University [YG2016ZD01]
- Science and Technology Ministry [2017YGB1302904]
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Objectives To identify potentially pathogenic mutations for tooth agenesis by whole-exome sequencing. Subjects and Methods Ten Chinese families including five families with ectodermal dysplasia (syndromic tooth agenesis) and five families with selective tooth agenesis were included. Whole-exome sequencing was performed using genomic DNA. Potentially pathogenic mutations were identified after data filtering and screening. The pathogenicity of novel variants was 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-kappa B activation was compromised by the identified mutations. The secretion of active EDA was also compromised detection 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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