title: Unusual presentation of a severe autosomal recessive anhydrotic ectodermal dysplasia with a novel mutation in the EDAR gene.
abstract: We report on an 18-year-old woman, born to first-cousin parents, presenting with a severe form of anhydrotic ectodermal dysplasia (EDA/HED). She had sparse hair, absent limb hair, absent sweating, episodes of hyperpyrexia, important hypodontia, and hyperconvex nails. She also showed unusual clinical manifestations such as an absence of breasts, a rudimentary extranumerary areola and nipple on the left side, and marked palmo-plantar hyperkeratosis. Light microscopy of skin biopsies showed orthokeratotic hyperkeratosis and absence of sweat glands. A novel homozygous mutation (IVS9 + 1G > A) in the EDAR gene was identified. This mutation results in a total absence of EDAR transcripts and consequently of the EDAR protein, which likely results in abolition of all ectodysplasin-mediated NF-kappaB signaling. This is the first complete loss-of-function mutation in the EDAR gene reported to date, which may explain the unusual presentation of HED in this patient, enlarging the clinical spectrum linked to the dysfunction of the ectodysplasin mediated NF-kappaB signaling.
authors.affiliation: Unité de Génétique Médicale, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon.
authors.forename: Hala
authors.initials: H
authors.lastname: Mégarbané
authors.forename: Céline
authors.initials: C
authors.lastname: Cluzeau
authors.forename: Christine
authors.initials: C
authors.lastname: Bodemer
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fraïtag
authors.forename: Myrna
authors.initials: M
authors.lastname: Chababi-Atallah
authors.forename: André
authors.initials: A
authors.lastname: Mégarbané
authors.forename: Asma
authors.initials: A
authors.lastname: Smahi
mesh_terms: D001940:Breast / Q000002:abnormalities; D053360:Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053331:Ectodysplasins / Q000378:metabolism; D053339:Edar Receptor / Q000235:genetics*; D005260:Female; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000175:diagnosis / Q000235:genetics; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017421:Sequence Analysis; D015398:Signal Transduction; D012868:Skin Abnormalities / Q000175:diagnosis / Q000235:genetics
chemical_list: C506018:EDA protein, human; D053331:Ectodysplasins; D053339:Edar Receptor; D016328:NF-kappa B