title: Novel EDA mutation in X-linked hypohidrotic ectodermal dysplasia and genotype-phenotype correlation.
abstract: OBJECTIVE
  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.
authors.affiliation: Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.|Department of Medical Genetics, Zhongshan School of Medicine and Center for Genome Research, Sun Yat-sen University, Guangzhou, China.
authors.forename: B
authors.initials: B
authors.lastname: Zeng
authors.affiliation: Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Lu
authors.affiliation: Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.affiliation: Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: D
authors.initials: D
authors.lastname: Yu
authors.affiliation: Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhao
mesh_terms: D000848:Anodontia / Q000209:etiology*; D004252:DNA Mutational Analysis; D053358:Ectodermal Dysplasia 1, Anhidrotic / Q000150:complications / Q000235:genetics*; D053331:Ectodysplasins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype
chemical_list: C506018:EDA protein, human; D053331:Ectodysplasins
keywords: EDAR; Ectodysplasin A; bioinformatics; hypodontia; missense; structural model