title: Mutations in EDARADD account for a small proportion of hypohidrotic ectodermal dysplasia cases.
abstract: BACKGROUND
  Hypohidrotic ectodermal dysplasia (HED) is characterized by abnormal development of the eccrine sweat glands, hair and teeth. The X-linked form of the disease, caused by mutations in the EDA gene, represents the majority of HED cases. Autosomal dominant and recessive forms occasionally occur and result from mutations in at least two other genes: EDAR and EDARADD. EDARADD interacts with the TAB2/TRAF6/TAK1 complex, which is necessary for NF-kappaB activation by EDAR.
  
  
  OBJECTIVE
  To determine frequency of EDARADD, TRAF6, TAB2 and TAK1 mutations in HED.
  
  
  METHODS
  We have screened 28 familial or sporadic HED cases with no mutations in the EDA and EDAR genes for EDARADD, TRAF6, TAB2 and TAK1 mutations.
  
  
  RESULTS
  We identified one EDARADD 6-bp homozygous in-frame deletion (c.402-407del, p.Thr135-Val136del) in a patient born to consanguineous parents. Functional studies showed that the p.Thr135-Val136del impaired the EDAR-EDARADD interaction and then severely inhibited NF-kappaB activity. In the remaining 27 patients, we failed to find causative mutations in EDARADD, or in TRAF6, TAB2 or TAK1.
  
  
  CONCLUSIONS
  Our study demonstrates that EDARADD mutations are not a frequent cause of HED, while mutations in TRAF6, TAB2 and TAK1 may not be implicated in this disease.
authors.affiliation: INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300 France.
authors.forename: N
authors.initials: N
authors.lastname: Chassaing
authors.forename: C
authors.initials: C
authors.lastname: Cluzeau
authors.forename: E
authors.initials: E
authors.lastname: Bal
authors.forename: P
authors.initials: P
authors.lastname: Guigue
authors.forename: M-C
authors.initials: MC
authors.lastname: Vincent
authors.forename: G
authors.initials: G
authors.lastname: Viot
authors.forename: D
authors.initials: D
authors.lastname: Ginisty
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: A
authors.initials: A
authors.lastname: Smahi
authors.forename: P
authors.initials: P
authors.lastname: Calvas
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis / Q000379:methods; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000378:metabolism; D053362:Edar-Associated Death Domain Protein / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D016415:Sequence Alignment; D013045:Species Specificity; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics; D015027:Zebrafish; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053362:Edar-Associated Death Domain Protein; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D048029:TNF Receptor-Associated Factor 6; D000099151:MAP Kinase Kinase Kinase 7; C506125:EDARADD protein, human; C410585:TAB2 protein, human