title: A novel missense mutation in the ectodysplasin-A (EDA) gene underlies X-linked recessive nonsyndromic hypodontia.
abstract: BACKGROUND
  Nonsyndromic hypodontia or congential absence of one or more permanent teeth is a common anomaly of dental development in humans. This condition may be inherited in an autosomal (dominant/recessive) or X-linked (dominant/recessive) mode. Mutations in three genes, PAX9, MSX1, and AXIN2, have been determined to be associated with autosomal dominant and recessive tooth agenesis. Recent studies in a few families showed that mutations in the ectodysplasin A (EDA) gene result in X-linked nonsyndromic hypodontia.
  
  
  METHODS
  Genotyping of a five-generation Pakistani family with X-linked isolated hypodontia having three affected men was carried out using EDA-linked polymorphic microsatellite markers on chromosome Xq12-q13.1. To screen for a mutation in the EDA gene, all of its coding exons and splice junction sites were PCR amplified from genomic DNA of affected and unaffected individuals of the family and sequenced directly in an ABI Prism 310 automated DNA sequencer.
  
  
  RESULTS
  We successfully mapped the affected locus to chromosome Xq12-q13.1, and found a novel missense mutation (c.993G>C) in the EDA gene in the affected men. The mutation causes substitution of glutamine with histidine (p.Q331H) in the tumor necrosis factor homology domain of EDA.
  
  
  CONCLUSIONS
  A mutation identified in this study extends the body of evidence implicating the EDA gene in X-linked nonsyndromic hypodontia and supports the role of EDA-EDAR-EDARADD signaling in the morphogenesis of teeth.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ayub
authors.forename: Fazal
authors.initials: F
authors.lastname: ur-Rehman
authors.forename: Masoom
authors.initials: M
authors.lastname: Yasinzai
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D002648:Child; D041321:Chromosomes, Human, X / Q000235:genetics*; D053358:Ectodermal Dysplasia 1, Anhidrotic / Q000235:genetics; D053331:Ectodysplasins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D015398:Signal Transduction / Q000235:genetics
chemical_list: D053331:Ectodysplasins