Novel EDA mutation in X-linked hypohidrotic ectodermal dysplasia and genotype-phenotype correlation

Oral Dis. 2015 Nov;21(8):994-1000. doi: 10.1111/odi.12376. Epub 2015 Oct 24.


Objectives: X-linked hypohidrotic ectodermal dysplasia (XLHED) is characterized by abnormalities of hair, teeth, and sweat glands, while non-syndromic hypodontia (NSH) affects only teeth. Mutations in Ectodysplasin A (EDA) underlie both XLHED and NSH. This study investigated the genetic causes of six hypohidrotic ectodermal dysplasia (HED) patients and genotype-phenotype correlation.

Methods: The EDA gene of six patients with HED was sequenced. Bioinformatics analysis and structural modeling for the mutations were performed. The records of 134 patients with XLHED and EDA-related NSH regarding numbers of missing permanent teeth from this study and 20 articles were reviewed. Nonparametric tests were used to analyze genotype-phenotype correlations.

Results: In four of the six patients, we identified a novel mutation c.852T>G (p.Phe284Leu) and three reported mutations: c.467G>A (p.Arg156His), c.776C>A (p.Ala259Glu), and c.871G>A (p.Gly291Arg). They were predicted to be pathogenic by bioinformatics analysis and structural modeling. Genotype-phenotype correlation analysis revealed that truncating mutations were associated with more missing teeth. Missense mutations and the mutations affecting the TNF homology domain were correlated with fewer missing teeth.

Conclusions: This study extended the mutation spectrum of XLHED and revealed the relationship between genotype and the number of missing permanent teeth.

Keywords: EDAR; Ectodysplasin A; bioinformatics; hypodontia; missense; structural model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anodontia / etiology*
  • DNA Mutational Analysis
  • Ectodermal Dysplasia 1, Anhidrotic / complications
  • Ectodermal Dysplasia 1, Anhidrotic / genetics*
  • Ectodysplasins / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Mutation, Missense
  • Pedigree
  • Phenotype


  • EDA protein, human
  • Ectodysplasins