title: A novel missense mutation in the gene EDARADD associated with an unusual phenotype of hypohidrotic ectodermal dysplasia.
abstract: Hypohidrotic ectodermal dysplasia (HED) is a rare disorder characterized by deficient development of structures derived from the ectoderm including hair, nails, eccrine glands, and teeth. HED forms that are caused by mutations in the genes EDA, EDAR, or EDARADD may show almost identical phenotypes, explained by a common signaling pathway. Proper interaction of the proteins encoded by these three genes is important for the activation of the NF-κB signaling pathway and subsequent transcription of the target genes. Mutations in the gene EDARADD are most rarely implicated in HED. Here we describe a novel missense mutation, c.367G>A (p.Asp123Asn), in this gene which did not appear to influence the interaction between EDAR and EDARADD proteins, but led to an impaired ability to activate NF-κB signaling. Female members of the affected family showed either unilateral or bilateral amazia. In addition, an affected girl developed bilateral ovarian teratomas, possibly associated with her genetic condition.
authors.affiliation: Department of Pediatrics, German Competence Center for Children with Ectodermal Dysplasias, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Wohlfart
authors.affiliation: Department of Pathology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Söder
authors.affiliation: Department of Genetics, INSERM U781, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Asma
authors.initials: A
authors.lastname: Smahi
authors.affiliation: Department of Pediatrics, German Competence Center for Children with Ectodermal Dysplasias, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Holm
authors.initials: H
authors.lastname: Schneider
mesh_terms: D000293:Adolescent; D001941:Breast Diseases / Q000235:genetics; D053358:Ectodermal Dysplasia 1, Anhidrotic / Q000235:genetics*; D053339:Edar Receptor / Q000235:genetics* / Q000378:metabolism; D053362:Edar-Associated Death Domain Protein / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006197:Hair / Q000254:growth & development; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D015398:Signal Transduction / Q000235:genetics; D013724:Teratoma / Q000235:genetics* / Q000473:pathology
chemical_list: C506008:EDAR protein, human; C506125:EDARADD protein, human; D053339:Edar Receptor; D053362:Edar-Associated Death Domain Protein; D016328:NF-kappa B
keywords: EDARADD; NF-κB signaling; amazia; hypohidrotic ectodermal dysplasia; teratoma