title: A missense mutation in the death domain of EDAR abolishes the interaction with EDARADD and underlies hypohidrotic ectodermal dysplasia.
abstract: BACKGROUND
  Hypohidrotic ectodermal dysplasia (HED) is a rare condition characterized by hypotrichosis, hypohidrosis and hypodontia. The disease shows X-linked recessive, autosomal-dominant or autosomal-recessive inheritance trait. X-linked form of HED is caused by mutations in the EDA gene, while autosomal forms are caused by mutations in either EDAR or EDARADD genes.
  
  
  METHODS
  We analyzed the DNA from a Japanese patient with HED through direct sequencing, and also performed functional studies for the mutation.
  
  
  RESULTS
  We identified a homozygous missense mutation c.1073G>A (p.R358Q) in the EDAR gene of the patient, which was a nonconservative amino acid substitution within the death domain of EDAR protein. We demonstrated that the p.R358Q mutant EDAR protein lost its affinity to EDARADD, leading to reduced activation of the downstream NF-κB.
  
  
  CONCLUSIONS
  Our data further suggest the crucial role of the EDAR signaling in development of hair, teeth, and sweat gland in humans.
authors.affiliation: Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Masui
authors.forename: Muhammad
authors.initials: M
authors.lastname: Farooq
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fujimoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Fujikawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ito
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shimomura
mesh_terms: D053358:Ectodermal Dysplasia 1, Anhidrotic / Q000235:genetics* / Q000378:metabolism; D053339:Edar Receptor / Q000235:genetics*; D053362:Edar-Associated Death Domain Protein / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D020125:Mutation, Missense; D016328:NF-kappa B / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015398:Signal Transduction
chemical_list: C506008:EDAR protein, human; C506125:EDARADD protein, human; D053339:Edar Receptor; D053362:Edar-Associated Death Domain Protein; D016328:NF-kappa B