Correlation between the phenotypes and genotypes of X-linked hypohidrotic ectodermal dysplasia and non-syndromic hypodontia caused by ectodysplasin-A mutations.

Mutations in the ectodysplasin-A (EDA) gene can cause both X-linked hypohidrotic ectodermal dysplasia (XLHED) and non-syndromic hypodontia (NSH). The correlation between the phenotypes and genotypes of these two conditions has yet to be described. In the present study, 27 non-consanguineous Chinese XLHED subjects were screened and 17 EDA mutations were identified. In order to investigate the correlation between genotype and phenotype, we also reviewed related studies on NSH subjects with confirmed EDA mutations and compared the differences in the clinical manifestations and EDA mutations of the two conditions. Tooth agenesis was observed in addition to abnormalities of other ectodermal organs. Tooth agenesis was more severe in XLHED subjects than in NSH subjects, and there were statistically significant differences in 10 tooth positions in the XLHED and NSH subjects, including canines, premolars, and molars. With the exception of one splicing mutation, all mutations in the NSH subjects were missense mutations, and these were most likely to be located in the tumor necrosis factor (TNF) domain. Further, more than half of the mutations in the XLHED subjects were speculated to be loss of function mutations, such as nonsense, insertion, and deletion mutations, and these mutations were distributed across all EDA domains. Our results show that there exists a correlation between the phenotypes and genotypes of XLHED and NSH subjects harboring EDA mutations. Further, our findings suggest that NSH is probably a variable expression of XLHED. This finding might be useful for clinical diagnosis and genetic counseling in clinical practice, and provides some insight into the different manifestations of EDA mutations in different ectodermal organs.