title: Novel missense mutation in the EDA gene in a family affected by oligodontia.
abstract: BACKGROUND
  Mutations in the EDA-EDAR-EDARADD genes and more recently, mutations in the WNT10A gene have been described as the cause of syndromic and nonsyndromic tooth agenesis concomitant with diverse abnormalities of ectodermally derived tissues.
  
  
  OBJECTIVE
  In the present investigation, two brothers presenting severe tooth agenesis (oligodontia) concomitant with subtle signs of ectodermal dysplasia (ED) symptoms, as well as six family relatives were analyzed for a causative mutation.
  
  
  METHODS
  Genomic DNA was isolated from saliva, and genetic screening performed via direct sequencing of PCR fragments covering the entire coding regions and the intron-exon junctions of the EDA, EDAR, EDARADD as well as the WNT10A genes. Mutation analysis was conducted using the Mutation Surveyor(®) Software.
  
  
  CONCLUSIONS
  We identified a novel G > A mutation located on exon 7 at nucleotide position c.866 in the EDA gene in both patients. The nucleotide change results in a substitution of arginine by histidine (p.Arg289His). According to the programs MutationTaster and PolyPhen2, this mutation is pathogenic. Based on a computerized protein structure analysis, we suggest that the change p.Arg289His in EDA impairs protein stabilization and thus might possibly be involved in the development of oligodontia concomitant with a mild ED phenotype.
authors.affiliation: Department of Orthodontics, Justus-Liebig-University of Giessen, Schlangenzahl 14, 35392, Giessen, Germany.
authors.forename: Gisela
authors.initials: G
authors.lastname: Ruiz-Heiland
authors.affiliation: Private practice, Lübeck, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Jabir
authors.affiliation: Institute of Biochemistry, Justus-Liebig-University of Giessen, Giessen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wende
authors.affiliation: Department of Dermatology, University Hospital Giessen and Marburg, Giessen, 35390, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Blecher
authors.affiliation: Department of Orthodontics, Justus-Liebig-University of Giessen, Schlangenzahl 14, 35392, Giessen, Germany.
authors.forename: Niko
authors.initials: N
authors.lastname: Bock
authors.affiliation: Department of Orthodontics, Justus-Liebig-University of Giessen, Schlangenzahl 14, 35392, Giessen, Germany. sabine.ruf@dentist.med.uni-giessen.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Ruf
mesh_terms: D000848:Anodontia / Q000175:diagnosis* / Q000235:genetics*; D053331:Ectodysplasins / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005858:Germany; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D035781:Siblings
chemical_list: C506018:EDA protein, human; D053331:Ectodysplasins; D005819:Genetic Markers
keywords: Ectodermal dysplasia; Ectodysplasin A; Non-syndromic hypodontia; Odontogenesis; Oligodontia