Clinical aspects of X-linked hypohidrotic ectodermal dysplasia.

Clarke, Angus; Phillips, David I. W.; Brown, Ryan; Harper, Peter S.

doi:10.1136/adc.62.10.989

Cited by 240 publications

(241 citation statements)

References 11 publications

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“…Ectodermal dysplasia encompasses a group of disorders characterized by defective development of ectodermally derived structures such as the hair, teeth, and exocrine glands (Clarke et al, 1987). EDA encodes the tumor necrosis factor (TNF) -like ligand EDA A1 (Srivastava et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Recombinant EDA or Sonic Hedgehog rescue the branching defect in Ectodysplasin A pathway mutant salivary glands in vitro

Wells

Mou

Headon

et al. 2010

Developmental Dynamics

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Hypohidrotic ectodermal dysplasia (HED) is characterized by defective ectodermal organ development. This includes the salivary glands (SGs), which have an important role in lubricating the oral cavity. In humans and mice, HED is caused by mutations in Ectodysplasin A (Eda) pathway genes. Various phenotypes of the mutant mouse Eda Ta/Ta , which lacks the ligand Eda, can be rescued by maternal injection or in vitro culture supplementation with recombinant EDA. However, the response of the SGs to this treatment has not been investigated. Here, we show that the submandibular glands (SMGs) of Eda Ta/Ta mice exhibit impaired branching morphogenesis, and that supplementation of Eda Ta/Ta SMG explants with recombinant EDA rescues the defect. Supplementation of Edar dlJ/dlJ SMGs with recombinant Sonic hedgehog (Shh) also rescues the defect, whereas treatment with recombinant Fgf8 does not. This work is the first to test the ability of putative Eda target molecules to rescue Eda pathway mutant SMGs. Developmental Dynamics 239:2674-2684,

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Section: Introductionmentioning

confidence: 99%

Recombinant EDA or Sonic Hedgehog rescue the branching defect in Ectodysplasin A pathway mutant salivary glands in vitro

Wells

Mou

Headon

et al. 2010

Developmental Dynamics

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“…There is significant morbidity and mortality in affected children as a result of hyperthermia resulting from their inability to sweat, combined with an increased risk of respiratory tract infections (Beahrs et al 1971; Soderholm and Kaitila 1985;Clarke et al 1987; Gilgenkrantz et al 1989). The human X-linked HED phenotype has been shown to be a result of mutations in the ectodysplasin (EDA; formerly EDI) gene (Zonana et al 1993; Kere et al 1996; Monreal et al 1998).…”

Section: Introductionmentioning

confidence: 99%

“…In X-linked hypohidrotic ectodermal dysplasia (XHED) in man (Mendelian inheritance in man (MIM) 305100), affected individuals have a developmental disorder characterized by sparse or absent hair, missing and/or malformed teeth, and hypoplastic eccrine glands (Beahrs et al 1971; Soderholm and Kaitila 1985;Clarke 1987;Clarke et al 1987; Kere et al 1996). There is significant morbidity and mortality in affected children as a result of hyperthermia resulting from their inability to sweat, combined with an increased risk of respiratory tract infections (Beahrs et al 1971; Soderholm and Kaitila 1985;Clarke et al 1987; Gilgenkrantz et al 1989).…”

Section: Introductionmentioning

confidence: 99%

Mutation identification in a canine model of X-linked ectodermal dysplasia

et al. 2005

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X-linked hypohidrotic ectodermal dysplasia (XHED), an inherited disease recognized in humans, mice, and cattle, is characterized by hypotrichosis, a reduced number or absence of sweat glands, and missing or malformed teeth. In a subset of affected individuals and animals, mutations in the EDA gene (formerly EDI), coding for ectodysplasin, have been found to cause this phenotype. Ectodysplasin is a homotrimeric transmembrane protein with an extracellular TNF-like domain, which has been shown to be involved in the morphogenesis of hair follicles and tooth buds during fetal development. Some human XHED patients also have concurrent immunodeficiency, due to mutations in the NF-κB essential modulator protein (IKBKG; formerly NEMO), which is also encoded on the X chromosome. In a breeding colony of dogs with XHED, immune system defects had been suspected because of frequent pulmonary infections and unexpected deaths resulting from pneumonia. To determine if defects in EDA or IKBKG cause XHED in the dogs, linkage analysis and sequencing experiments were performed. A polymorphic marker near the canine EDA gene showed significant linkage to XHED. The canine EDA gene was sequenced and a nucleotide substitution (G to A) in the splice acceptor site of intron 8 was detected in affected dogs. In the presence of the A residue, a cryptic acceptor site within exon 9 is used, leading to a frame shift and use of a premature stop codon that truncates the translation of both isoforms, EDA-A1 and EDA-A2, resulting in the absence of the TNF-like homology domain, the receptorbinding site of ectodysplasin.

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“…When this condition goes unrecognized, there is a 30% mortality rate due to hypothermia during the first 2 years of life (2). The XLHED locus, ED-1, encodes a multidomain transmembrane protein, ectodysplasin-A (EDA) (1,(3)(4)(5)(6).…”

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confidence: 99%