When a horse is born with naked foal syndrome (NFS), it will likely die early. This genetic skin condition affects the Akhal-Teke horse breed from Turkmenistan, which is known for its speed, endurance, and intelligence. Worryingly, the incidence of NFS seems to be increasing. Although breeders have been aware of NFS for over 75 years, it has never been scientifically described, and and while it’s known to be an autosomal recessive disease, its exact genetic cause was unknown until now. In the April issue of G3, Bauer et al. provide a detailed characterization of NFS and report finding the genetic determinant of the disease.
Bauer et al. examined two horses afflicted with NFS. One horse was still alive at almost three years of age, which is rare as most affected horses die within days to months, and had growth delays, sparse body hair, and dry skin. The second horse examined had been euthanized at 21 days of age because of a leg fracture, so the researchers were able to perform a necropsy. The exam revealed an area of fluid buildup in the brain called a hydrocephalus, as well as heart and immune system abnormalities, but the researchers do not think that these defects are a result of NFS. If more NFS-affected foals are also found to have these abnormalities, though, they may be worth investigating further.
To identify the genetic cause of NFS, the researchers sequenced the entire genomes of the two affected horses, two known carriers, and 75 unaffected controls. They found that a nonsense variant of a single gene, ST14, was present in the NFS-affected and carrier horse genomes. ST14 encodes a type II serine protease, sometimes called matriptase, which is known to be involved in epidermal development. In mice, pups with the mouse version of the gene (St14) knocked out have dry and red skin that lacks its normal barrier functions. Without this protection, the pups rapidly lose fluid through the skin, resulting in dehydration and death within two days of birth. Although this doesn’t seem to be the cause for NFS’s lethality in horses, the fact that both affected horses and mice exhibit major skin defects lends credibility to the researchers’ conclusion that mutations in ST14 cause NFS.
This discovery will allow breeders to screen for the mutation, eliminating the disease in their horse lines. Interestingly, variants of the same gene cause autosomal recessive congenital ichthyosis 11 (ARCI11) in humans, so horses with NFS could serve as a large animal model for the disease.
Bauer, A.; Hiemesch, T.; Jagannathan, V.; Neuditschko, M.; Bachmann, I.; Rieder, S.; Mikko, S.; Penedo, M.; Tarasova, N.; Vitková, M.; Sirtori, N.; Roccabianca, P.; Leeb, T.; Welle, M. A Nonsense Variant in the ST14 Gene in Akhal-Teke Horses with Naked Foal Syndrome.
G3, 7(4), 1315-1321.