Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Autosomal dominant anhidrotic ectodermal dysplasias at the EDARADD locus
Human Mutation, Volume 28, No. 7, Year 2007
Notification
URL copied to clipboard!
Description
Anhidrotic ectodermal dysplasia (EDA) is a disorder of ectodermal differentiation characterized by sparse hair, abnormal or missing teeth, and inability to sweat. X-linked EDA is the most common form, caused by mutations in the EDA gene, which encodes ectodysplasin, a member of the tumor necrosis factor (TNF) family. Autosomal dominant and recessive forms of EDA have been also described and are accounted for by two genes. Mutations in EDAR, encoding a TNF receptor (EDAR) cause both dominant and recessive forms. In addition, mutations in a recently identified gene, EDARADD, encoding EDAR-associated death domain (EDARADD) have been shown to cause autosomal recessive EDA. Here, we report a large Moroccan family with an autosomal dominant EDA. We mapped the disease gene to chromosome 1q42.2-q43, and identified a novel missense mutation in the EDARADD gene (c.335T>G, p.Leu112Arg). Thus, the EDARADD gene accounts for both recessive and dominant EDA. EDAR is activated by its ligand, ectodysplasin, and uses EDARADD to build an intracellular complex and activate nuclear factor kappa B (NF-κB). We compared the functional consequences of the dominant (p.Leu112Arg) and recessive mutation (p.Glu142Lys), which both occurred in the death domain (DD) of EDARADD. We demonstrated that the p.Leu112Arg mutation completely abrogated NF-κB activation, whereas the p.Glu142Lys retained the ability to significantly activate the NF-κB pathway. The p.Leu112Arg mutation is probably a dominant negative form as its cotransfection impaired the wild-type EDARADD's ability to activate NF-κB. Our results confirm that NF-κB activation is impaired in EDA and support the role of EDARADD DD as a downstream effector of EDAR signaling. © 2007 Wiley-Liss, Inc.
Authors & Co-Authors
Bal, Elodie
France, Paris
Hôpital Necker Enfants Malades
Baala, Lekbir
France, Paris
Hôpital Necker Enfants Malades
Cluzeau, C.
France, Paris
Hôpital Necker Enfants Malades
El-Kerch, Fatiha
Morocco, Agdal Rabat
Institut National D'hygiène
Ouldim, Karim
Morocco, Agdal Rabat
Institut National D'hygiène
Hadj-Rabia, Smaïl
France, Paris
Hôpital Necker Enfants Malades
Bodemer, Christine
France, Paris
Hôpital Necker Enfants Malades
Munnich, A.
France, Paris
Hôpital Necker Enfants Malades
Courtois, Gilles
France, Paris
Hôpital Saint-louis
Sefiani, Abdelaziz
Morocco, Agdal Rabat
Institut National D'hygiène
Smahi, A.
France, Paris
Hôpital Necker Enfants Malades
Statistics
Citations: 88
Authors: 11
Affiliations: 3
Identifiers
Doi:
10.1002/humu.20500
ISSN:
10597794
Research Areas
Cancer
Genetics And Genomics