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.

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.

Breeds: Chinese Crested Dog, Mexican Hairless Dog (Xoloitzcuintli), Peruvian Hairless Dog (Inca Hairless).

Associated gene: