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

ABSTRACT

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.