In other species: pig

Categories: Integument (skin) phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 607591 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2017

Cross-species summary: Recessive form of lack of hair growth

Species-specific name: Recessive hairlessness, congenital alopecia

Species-specific description: See also OMIA:000323-9615 : Ectodermal dysplasia in Canis lupus familiaris (dog) for a different genetic form of hairless dogs due to variants in the FOXI3 gene.

Inheritance: Sponenberg et al. (1988) reported matings of haired American Rat Terriers and American Hairless Terriers (AHT, the first AHT is from a litter American Rat Terriers) and concluded that the results were consistent with an autosomal recessive inheritance.

Mapping: Parker et al. (2017) mapped this trait to a region "greater than 4.8 Mb from chr29 : 15973319–20794824 in the CanFam3.1 assembly".

Molecular basis: Parker et al. (2017) identified a likely causal mutation ("SGK3^Val96GlyfsTer50"): a "deletion [that] removes four bases (TTAG) from chr29 : 16366702–16366705 within exon 4 of the serum/glucocorticoid regulated kinase family member 3 gene (SGK3). This deletion alters the reading frame of the protein at amino acid 96 creating a new protein sequence for 50 amino acids and a premature stop at amino acid 157. This mutation is predicted to knock out the original function of the gene as it removes the entire STKc_SGK3 catalytic domain for which the gene is named. . . . the 4 bp deletion . . . was resequenced in 12 hairless AHT [American Hairless Terrier] and four coated Rat Terriers . . . . All hairless AHT were found to have two copies of the mutation, while the four coated Rat Terriers were wild-type at both alleles". Hytönen and Lohi (2019) reported "a 1-bp insertion in exon 2 of SGK3 . . . [resulting] . . . in a predicted frameshift and very early truncation (49/490 amino acids) of the SGK3 protein." as a likely causal variant in Scottish Deerhounds. Parker et al. (2020) provided independent confirmation of this likely causal variant in Scottish Deerhounds.

Clinical features: American Hairless Terrier puppies are born with a sparse downy coat of hair that is lost within the first months of life and not replaced. Whiskers and eyebrows are present (Sponenberg et al., 1988). The 2 Scottish Deerhound puppies reported by Hytönen & Lohi (2019) "were born with sparse hair, but lost it completely within the first 2 months of life." Parker et al. (2020) identified the condition in an independent Scottish Deerhound family and noted that "puppies displayed either a normal, full coat or a sparse and receding coat ... . In those who initially had hair but went bald, the coat progressively thinned early in life and was completely gone by five weeks." Hairless dogs in both breeds are described as otherwise generally healthy (Parker et al., 2017; Hytönen & Lohi, 2019; Parker et al., 2020), but hairlessness is considered non desirable in the Scottish Deerhound.

Prevalence: Hytönen and Lohi (2019) "genotyped the SGK3:c.137_138insT variant . . . in a cohort of Scottish Deerhounds (n = 66) containing two affected dogs, two unaffected dogs, which had produced affected progeny, and 62 other unaffected dogs from our biobank. Both affected dogs were homozygous for the variant and the two obligate carriers were heterozygous, while the rest of the dogs were either heterozygous (n = 6) or homozygous for the wild-type allele (n = 56). These results demonstrate a full segregation of the variant with the disease and indicate a 12% carrier frequency in the studied cohort. We screened the variant also in a related breed, Irish Wolfhound (n = 91), but did not find any carriers, suggesting a breed-specific variant in SD population."

Breeds: American Hairless Terrier (Dog) (VBO_0200049), Rat Terrier (Dog) (VBO_0201125), Scottish Deerhound (Dog) (VBO_0201195).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: