In other species: pig

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2017

Cross-species summary: Recessive form of hair loss.

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.

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, Scottish Deerhound.

Associated gene: