Two Novel Mutations in Ectodysplasin-A Identified in Syndromic Tooth Agenesis.

OBJECTIVE

To discover novel ectodysplasin-A (EDA) and wingless-type MMTV integration site family, member 10A (WNT10A) mutations in tooth agenesis (TA) patients.

STUDY DESIGN

Case series.

PLACE AND DURATION OF STUDY

Guanghua School of Stomatology, Guangzhou, China, from March 2018 to August 2020.

METHODOLOGY

EDA and WNT10A were analysed in eleven TA families by PCR and Sanger sequencing. Bioinformatics and structure modelling analyses were performed after identifying different variants, to predict the resulting conformational alterations in WNT10A and EDA.

RESULTS

Two novel mutations (c.796C>A (p.L266I), c.769G>A (p.G257R)) in EDA and two reported mutations (c.637G>A (p.G213S), c.511C>T (p.R171C))in WNT 10A were detected. Combined with the 3D structural analysis, we discovered a correlation between alterations in hydrogen bond formation and the observed phenotypes, potentially affecting protein binding.

CONCLUSIONS

The mutations were predicted to be pathogenic through bioinformatics analyses. In addition, by identifying novel mutations, our knowledge regarding the TA spectrum and tooth development was considerably expanded.

KEY WORDS

Anodontia, EDA, WNT 10A, Whole exome sequencing, Odontogenesis.