OMIA:000323-9615 : Ectodermal dysplasia in Canis lupus familiaris (dog)
In other species: chicken
Categories: Integument (skin) phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 305100 (trait)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal incomplete dominant
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2008
Cross-species summary: Hairless
Species-specific name: Canine ectodermal dysplasia
Species-specific symbol: CED
Species-specific description: Canine ectodermal dysplasia is characterized by hairlessness and missing or abnormally shaped teeth. Early breeding studies demonstrated embryonal lethality of homozygous mutant animals and an autosomal semidominant mode of inheritance (Robinson, 1985). In detail, homozygous mutant embryos die very early during pregnancy and are resorbed, heterozygous dogs exhibit the ectodermal dysplasia phenotype, which is characteristic of several hairless dog breeds. Later studies showed the trait is caused by a 7 bp duplication in exon 1 of FOXI3. This is a desired trait in several breeds, including the Peruvian Inca, Mexican Hairless, and Chinese Crested Dog.
Edited by Dr. Margret Casal
Mapping: By conducting a GWAS on "20 hairless and 19 coated Chinese Crested dogs", each of which had been genotyped with the Affymetrix v2 SNP chip (yielding 12,353 informative SNPs) Drögemüller et al. (2008) highlighted a single SNP on chromosome CFA17. Fine-mapping reduced the candidate region to "a 102-kb interval between positions 41,045,331 and 41,147,100 on CFA 17", containing only two predicted genes.
Molecular basis: By sequencing the more likely of the two positional candidate genes (see Mapping section), Drögemüller et al. (2008) showed that this disorder is due to a 7-bp tandem duplication in exon 1 of FOXI3, a member of the family of forkhead box transcription factor genes. This gene was previously unknown to contribute to the development of ectodermal structures.
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: Affected dogs have varying degrees of hairlessness but most commonly, almost the entire body is affected. Depending on the breed, there will be tufts of hair on the distal limbs and the top of the head. Some dogs have very abnormal teeth, many of which are missing. Others appear to have only mild abnormalities. Toenails may be long and brittle. Neonatal deaths are more common in hairless pups than in their normal littermates. Wiener et al. (2013) provided extensive details of the clinical and histological differences between the "three subphenotypes (true hairless, semi-coated and powderpuffs) of Chinese crested dogs" and also "clearly demonstrated distinct differences between the canine ectodermal dysplasia in Chinese crested dogs and dogs with X-linked ectodermal dysplasia".
Pathology: Histological examination of hairless skin and foot pads shows an absence of hair follicles, adnexal structures, and eccrine glands.
Prevalence: The condition is prevalent in specific breeds. It is considered a desired trait.
Control: As this is a desired trait, no control is needed. However in some breeds, such as the Chinese crested, breeding hairless individuals to each other may result in smaller litter sizes as the presence of a double dose of the mutation in homozygote puppies leads to prenatal mortality.
Genetic testing: Mutation testing is available.
Chinese Crested (Dog) (VBO_0200345),
Peruvian Hairless Dog (Dog) (VBO_0201004),
Xoloitzcuintli (Dog) (VBO_0201436).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|FOXI3||forkhead box I3||Canis lupus familiaris||17||NC_051821.1 (38764819..38768812)||FOXI3||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|571||Chinese Crested (Dog) Peruvian Hairless Dog (Dog) Xoloitzcuintli (Dog)||Ectodermal dysplasia||FOXI3||insertion, small (<=20)||Naturally occurring variant||ROS_Cfam_1.0||17||g.38764875_38764881dup||c.57_63dup||p.(A23Rfs*219)||NM_001135646.1; NP_001129118.1||2008||18787161|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2023||Welle, M.M. :|
|Canine noninflammatory alopecia: An approach to its classification and a diagnostic aid. Vet Pathol :3009858231170295, 2023. Pubmed reference: 37191329. DOI: 10.1177/03009858231170295.|
|2017||Kupczik, K., Cagan, A., Brauer, S., Fischer, M.S. :|
|The dental phenotype of hairless dogs with FOXI3 haploinsufficiency. Sci Rep 7:5459, 2017. Pubmed reference: 28710361. DOI: 10.1038/s41598-017-05764-5.|
|Parker, H.G., Harris, A., Dreger, D.L., Davis, B.W., Ostrander, E.A. :|
|The bald and the beautiful: hairlessness in domestic dog breeds. Philos Trans R Soc Lond B Biol Sci 372:20150488, 2017. Pubmed reference: 27994129. DOI: 10.1098/rstb.2015.0488.|
|2013||Shirokova, V., Jussila, M., Hytönen, M.K., Perälä, N., Drögemüller, C., Leeb, T., Lohi, H., Sainio, K., Thesleff, I., Mikkola, M.L. :|
|Expression of Foxi3 is regulated by ectodysplasin in skin appendage placodes. Dev Dyn 242:593-603, 2013. Pubmed reference: 23441037. DOI: 10.1002/dvdy.23952.|
|Wiener, D.J., Gurtner, C., Panakova, L., Mausberg, T.B., Müller, E.J., Drögemüller, C., Leeb, T., Welle, M.M. :|
|Clinical and histological characterization of hair coat and glandular tissue of Chinese crested dogs. Vet Dermatol 24:274-e62, 2013. Pubmed reference: 23413772. DOI: 10.1111/vde.12008.|
|2008||Drögemüller, C., Karlsson, E.K., Hytönen, M.K., Perloski, M., Dolf, G., Sainio, K., Lohi, H., Lindblad-Toh, K., Leeb, T. :|
|A mutation in hairless dogs implicates FOXI3 in ectodermal development. Science 321:1462, 2008. Pubmed reference: 18787161. DOI: 10.1126/science.1162525.|
|2005||O'Brien, DP., Johnson, GS., Schnabel, RD., Khan, S., Coates, JR., Johnson, GC., Taylor, JF. :|
|Genetic mapping of canine multiple system degeneration and ectodermal dysplasia loci. J Hered 96:727-34, 2005. Pubmed reference: 15958791. DOI: 10.1093/jhered/esi086.|
|Sander, P., Drögemüller, C., Cadieu, E., André, C., Leeb, T. :|
|Analysis of the canine EDAR gene and exclusion as a candidate for the hairless phenotype in the Chinese Crested dog. Anim Genet 36:168-71, 2005. Pubmed reference: 15771734. DOI: 10.1111/j.1365-2052.2005.01242.x.|
|1993||Kimura, T., Ohshima, S., Doi, K. :|
|The Inheritance and Breeding Results of Hairless Descendants of Mexican Hairless Dogs Laboratory Animals 27:55-58, 1993. Pubmed reference: 8437436.|
|1985||Robinson, R. :|
|Chinese crested dog Journal of Heredity 76:217-218, 1985. Pubmed reference: 3998444.|
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