Br J Dermatol. 2010 May;162(5):1044-8. Epub 2010 Mar 5.

Mutations in EDARADD account for a small proportion of hypohidrotic ectodermal dysplasia cases.External

Chassaing, N., Cluzeau, C., Bal, E., Guigue, P., Vincent, M. C., Viot, G., Ginisty, D., Munnich, A., Smahi, A., Calvas, P.,
--- - INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300 France.
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. OBJECTIVES: To determine frequency of EDARADD, TRAF6, TAB2 and TAK1 mutations in HED. MATERIALS AND 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.
PMID: 20222921External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD EDAR Link EDARADD Co-immunoprecipitation HEK293 Not specified Not specified Human Not specified 20222921
(Link: click this icon to show interactions only between the two corresponding DDs)