EDAR mutation in autosomal dominant hypohidrotic ectodermal dysplasia in two Swedish families.
Open accessAbstract
Background: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder characterized by defective development of teeth, hair, nails and eccrine sweat glands. Both autosomal dominant and autosomal recessive forms of HED have previously been linked to mutations in the ectodysplasin 1 anhidrotic receptor (EDAR) protein that plays an important role during embryogenesis. Methods: The coding DNA sequence of the EDAR gene was analyzed in two large Swedish three-generational families with autosomal dominant HED. Results: A non-sense C to T mutation in exon 12 was identified in both families. This disease-specific mutation changes an arginine amino acid in position 358 of the EDAR protein into a stop codon (p.Arg358X), thereby truncating the protein. In addition to the causative mutation two polymorphisms, not associated with the HED disorder, were also found in the EDAR gene. Conclusion: The finding of the p.Arg358X mutation in the Swedish families is the first corroboration of a previously described observation in an American family. Thus, our study strengthens the role of this particular mutation in the aetiology of autosomal dominant HED and confirms the importance of EDAR for the development of HED.
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These mutations were found at identical positions as seen in familial cases of HED in humans.
“These mutations were found at identical positions as seen in familial cases of HED in humans (Figure 3B, E; [11],[12].”
From Zebrafish eda and edar Mutants Reveal Conserved and Ancestral Roles of Ectodysplasin Signaling in Vertebrates (2008) · cites this paper as [12]
The Discussion reports that the EDAR p.Arg358X mutation in two Swedish families is identical to one previously described in an American family with HED. It does not establish that the unspecified multiple mutations referred to as “these mutations” occur at identical positions in human familial cases. (LLM, conf=0.78)
Experimental — accuracy not yet measuredAutosomal dominant HED in humans caused by mutation of EDAR within the death domain displays a large degree of phenotypic variability.
“Autosomal dominant HED in humans caused by mutation of EDAR within the death domain displays a large degree of phenotypic variability [12].”
From Zebrafish eda and edar Mutants Reveal Conserved and Ancestral Roles of Ectodysplasin Signaling in Vertebrates (2008) · cites this paper as [12]
The Discussion reports variable symptoms, including differences among people carrying the same EDAR mutation. It also specifies that the p.Arg358X mutation truncates EDAR at amino acid 358, abolishing the death domain at amino acids 367–431. Thus the variability is supported, but the mutation is not located within the death domain as claimed. (LLM, conf=0.88)
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Cites
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Harris, M. P., Rohner, N., Schwarz, H., Perathoner, S., Konstantinidis, P., & Nüsslein-Volhard, C. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000206 · Cited by 224 · see citing works
Orodental manifestations in ectodermal dysplasia—A review
Bergendal, B. (2014) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.36571 · Cited by 65 · see citing works
- Authors
- Lind, L. K., Stecksén-Blicks, C., Lejon, K., & Schmitt-Egenolf, M.
- Affiliations
- Umeå University (SE)
- ORCID
- Lejon, Kristina
- Venue
- BMC Medical Genetics
- Published
- 2006-11-24
- Volume
- 7
- Issue
- 1
- Pages
- 80-80
- ISSN
- 1471-2350 (ISSN-L)
- PMC
- PMC1684249
- OpenAlex
- W2124935184
- Cited by
- 39
- References
- 2
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2019: 1 · 2017: 1 · 2015: 4 · 2014: 4 · 2013: 1 · 2012: 4
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Medical Genetics (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
- Keywords
- hypohidrotic ectodermal dysplasia, EDAR gene, autosomal dominant inheritance, nonsense mutation, protein truncation, genetic aetiology, Swedish families, polymorphism
- MeSH terms
- Abnormalities, Multiple, DNA Mutational Analysis, Ectodermal Dysplasia, Family Health, Female, Genes, Dominant, Humans, Hypohidrosis, Male, Mutation, Pedigree, Polymorphism, Genetic, Sweden, Codon, Nonsense, Edar Receptor
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