Categories: Integument (skin) phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 602400 (trait) , 606797 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2017

Species-specific symbol: NFS

History: Bauer et al. (2017): "The first records of hairless Akhal-Teke foals date back to 1938 and since then the number of such foals has increased steadily. Many horses with NFS might have been registered as stillborn or weak born or not been reported at all (Kuznetcova et al. 2006)."

Inheritance: Bauer et al. (2017): "NFS is inherited as a monogenic autosomal recessive trait."

Mapping: Linkage mapping using just three affected horses and their four parents, each genotyped with the Affymetrix equine 670 k SNP chip, followed by homozygosity mapping of the same three affected horses, enabled Bauer et al. (2017) to map "the disease causing genetic variant to two segments on chromosomes 7 and 27 in the equine genome". (FN thanks Emily Rogers, who provided the basis for the rewording of this entry, working under the supervision of Professor Ernie Bailey; 24 April 2020)

Molecular basis: Bauer et al. (2017): "Whole genome sequencing of two affected horses, two obligate carriers, and 75 control horses from other breeds revealed a single non-synonymous genetic variant on the chromosome 7 segment that was perfectly associated with NFS. The affected horses were homozygous for ST14:c.388G>T, a nonsense variant that truncates more than 80% of the open reading frame of the ST14 gene (p.Glu130*). The variant leads to partial nonsense mediated decay of the mutant transcript." Transcript and protein sites correspond to the equine ST14 gene references XM_005611718.2 (cDNA) and XP_005611775.1 (protein). (FN thanks Emily Rogers, who provided the last sentence, working under the supervision of Professor Ernie Bailey; 24 April 2020)

Clinical features: Bauer et al. (2017): "Affected horses had almost no hair and showed a mild ichthyosis. So far, all known NFS affected horses died between a few weeks and 3 years of age. It is not clear whether a specific pathology caused the premature deaths." Bauer et al. (2017) noted similarities to ST14 defects in other species: “Taken together, the ST14 gene has essential roles in the interfollicular epidermis by contributing to epidermal barrier formation as well as for hair follicle development. The observed phenotype in NFS-affected horses resembles the group of heterogeneous phenotypes caused by ST14 variants in humans and mice. However, in horses with NFS, the degree of alopecia is more severe than in human patients, whereas the ichthyosis is less pronounced, and suggested mainly by the clinical picture.” (FN thanks Emily Rogers, who provided all but the first sentence of this entry, working under the supervision of Professor Ernie Bailey; 24 April 2020)

Prevalence: The variant c.388G>T was homozygous in 5 affected horses and heterozygous in 10 obligate carriers. Testing of 191 other Akhal-Teke horses identified 165 homozygous for the reference sequence and 26 heterozygous for c.388G>T. This variant was not found among 400 horses of other breeds. (Bauer et al., 2017) (FN thanks Emily Rogers, who provided this contribution, working under the supervision of Professor Ernie Bailey; 24 April 2020)

Breed: Akhal-Teke (Horse) (VBO_0000894).
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: