Mutations in<i>EDARADD</i>account for a small proportion of hypohidrotic ectodermal dysplasia cases

Chassaing, Nicolas; Cluzeau, Céline; E, Bal; Guigue, Philippe; Mc, Vincent; Viot, Géraldine; Ginisty, Danièle; Münnich, Arnold; Smahi, Asma; Calvas, Patrick

doi:10.1111/j.1365-2133.2010.09670.x

Cited by 31 publications

(21 citation statements)

References 28 publications

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“…), 12 no mutations in its human equivalent have been described, excluding a single sequence variant 479T>G (Met160Thr) reported in a patient with HED in whom a pathogenic mutation in EDARADD was detected. However, this sequence abnormality was not responsible for symptoms of HED as it was also present in an asymptomatic brother of the patient 13 …”

Section: Discussionmentioning

confidence: 86%

A rare heterozygous TRAF6 variant is associated with hypohidrotic ectodermal dysplasia

Wisniewski

Trzeciak

2012

British Journal of Dermatology

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Section: Discussionmentioning

confidence: 86%

A rare heterozygous TRAF6 variant is associated with hypohidrotic ectodermal dysplasia

Wisniewski

Trzeciak

2012

British Journal of Dermatology

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“…To date, four EDARADD mutations have been found in a subset of human HED, one leads to autosomal dominant inheritance (Leu112Arg) [26], while the others lead to autosomal recessive inheritance (Glu142Lys, Pro121Ser, and Thr135-Val136del) [6,28,29]. All of these mutations are located in the DD and functional analyses showed that they resulted in the failure of EDARADD to interact with EDAR and to activate NF-κB.…”

Section: Discussionmentioning

confidence: 99%

A rat model of hypohidrotic ectodermal dysplasia carries a missense mutation in the Edaradd gene

et al. 2011

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BackgroundHypohidrotic ectodermal dysplasia (HED) is a congenital disorder characterized by sparse hair, oligodontia, and inability to sweat. It is caused by mutations in any of three Eda pathway genes: ectodysplasin (Eda), Eda receptor (Edar), and Edar-associated death domain (Edaradd), which encode ligand, receptor, and intracellular adaptor molecule, respectively. The Eda signaling pathway activates NF-κB, which is central to ectodermal differentiation. Although the causative genes and the molecular pathway affecting HED have been identified, no curative treatment for HED has been established. Previously, we found a rat spontaneous mutation that caused defects in hair follicles and named it sparse-and-wavy (swh). Here, we have established the swh rat as the first rat model of HED and successfully identified the swh mutation.ResultsThe swh/swh rat showed sparse hair, abnormal morphology of teeth, and absence of sweat glands. The ectoderm-derived glands, meibomian, preputial, and tongue glands, were absent. We mapped the swh mutation to the most telomeric part of rat Chr 7 and found a Pro153Ser missense mutation in the Edaradd gene. This mutation was located in the death domain of EDARADD, which is crucial for signal transduction and resulted in failure to activate NF-κB.ConclusionsThese findings suggest that swh is a loss-of-function mutation in the rat Edaradd and indicate that the swh/swh rat would be an excellent animal model of HED that could be used to investigate the pathological basis of the disease and the development of new therapies.

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“…Mutations in the gene encoding the ligand (EDA) are believed to be the most common cause of ED involving the hair, teeth, skin, and sweat glands [Kere et al, 1996;Monreal et al, 1998]. Similar phenotypes are also described in patients with mutations in the EDA receptor (EDAR) gene or, in rare cases, the downstream signaling mediator EDAR-associated death domain (EDARADD) gene [Headon et al, 2001;Chassaing et al, 2006Chassaing et al, , 2010Bailleul-Forestier et al, 2008b;Mikkola 2009]. Mutations in the EDA and EDAR genes have also been shown to cause isolated hypodontia [Tao et al, 2006;Fan et al, 2008;Han et al, 2008;Rasool et al, 2008;Azeem et al, 2009;Mues et al, 2009a;Nieminen, 2009;Song et al, 2009].…”

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confidence: 94%

Isolated oligodontia associated with mutations in EDARADD, AXIN2, MSX1, and PAX9 genes

Bergendal¹,

Klar²,

Stecksén‐Blicks³

et al. 2011

American J of Med Genetics Pt A

127

104

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Oligodontia is defined as the congenital lack of six or more permanent teeth, excluding third molars. Oligodontia as well as hypodontia (lack of one or more permanent teeth) are highly heritable conditions associated with mutations in the AXIN2, MSX1, PAX9, EDA, and EDAR genes. Here we define the prevalence of mutations in the AXIN2, MSX1, PAX9, EDA, and EDAR genes, and the novel candidate gene EDARADD in a cohort of 93 Swedish probands with non-syndromic, isolated oligodontia. Mutation screening was performed using denaturing gradient gel electrophoresis and DNA sequence analysis. Analyses of the coding sequences of the six genes showed sequence alterations predicted to be damaging or potentially damaging in ten of 93 probands (10.8%). Mutations were identified in the EDARADD (n = 1), AXIN2 (n = 3), MSX1 (n = 2), and PAX9 (n = 4) genes, respectively. None of the 10 probands with mutations had other self-reported symptoms from ectodermal tissues. The oral parameters were similar when comparing individuals with and without mutations but a family history of oligodontia was three times more frequent for probands with mutations. EDARADD mutations have previously been reported in a few families segregating hypohidrotic ectodermal dysplasia and this is, to our knowledge, the first report of an EDARADD mutation associated with isolated oligodontia.

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Mutations inEDARADDaccount for a small proportion of hypohidrotic ectodermal dysplasia cases

Abstract: 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.

Cited by 31 publications

References 28 publications

A rare heterozygous TRAF6 variant is associated with hypohidrotic ectodermal dysplasia

A rare heterozygous TRAF6 variant is associated with hypohidrotic ectodermal dysplasia

A rat model of hypohidrotic ectodermal dysplasia carries a missense mutation in the Edaradd gene

Isolated oligodontia associated with mutations in EDARADD, AXIN2, MSX1, and PAX9 genes

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