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.
- American Journal of Medical Genetics Part A 07/2009; 149A(7):1612-3. DOI:10.1002/ajmg.a.32945 · 2.05 Impact Factor
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ABSTRACT: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder characterised by sparse hair, lack of sweat glands and malformation of teeth. The X-linked form of the disease, caused by mutations in the EDA gene, represents the majority of HED cases. Autosomal forms result from mutations in either the EDAR or the EDARADD gene. The X-linked and autosomal forms are phenotypically indistinguishable. For the purpose of genetic counselling, it is, therefore, important to know which gene is involved. In this study, we ascertained a Spanish family demonstrating the autosomal recessive form of HED. Affected individuals in the family showed the characteristic features of HED, including fine and sparse scalp hair, sparse eyebrows and eyelashes, periorbital hyperpigmentation, prominent lips, hypodontia and conical teeth, reduced sweating, and dry and thin skin. Sequence analysis of the EDAR gene revealed a novel compound heterozygous mutation [c.52-2A>G; c.212G>A (p.Cys71Tyr)]. Our finding extends the body of evidence that supports the significance of the EDAR signalling pathway in the ectodermal morphogenesis.Archives for Dermatological Research 05/2010; 302(4):307-10. DOI:10.1007/s00403-009-1013-z · 2.27 Impact Factor
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ABSTRACT: The Edar subfamily of TNFRs includes three receptors, Edar, Troy, and Xedar, with similar extracellular but unrelated intracellular domains. All three receptors are expressed in the embryonic ectoderm and/or its appendages, such as hair follicle, tooth, and sweat and mammary gland. While the function of the Edar pathway, mutated in human hypohidrotic ectodermal syndrome (HED), has been conserved during vertebrate evolution, considerably less is known about the physiological role of Troy and Xedar. Research on the Edar pathway has focused on hair follicle and tooth biology, but recent progress has been made in uncovering its relevance in morphogenesis of glandular appendages as well.Advances in Experimental Medicine and Biology 01/2011; 691:23-33. DOI:10.1007/978-1-4419-6612-4_3 · 2.01 Impact Factor