A Nonsense Variant in the ST14 Gene in Akhal-Teke Horses with Naked Foal Syndrome.

Naked foal syndrome (NFS) is a genodermatosis in the Akhal-Teke horse breed. We provide the first scientific description of this phenotype. 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. NFS is inherited as a monogenic autosomal recessive trait. We mapped the disease causing genetic variant to two segments on chromosomes 7 and 27 in the equine genome. 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. Genetic variants in the ST14 gene are responsible for autosomal recessive congenital ichthyosis 11 in humans. Thus, the identified equine ST14:c.388G>T variant is an excellent candidate causative variant for NFS and the affected horses represent a large animal model for a known human genodermatosis. Our findings will enable genetic testing to avoid the non-intentional breeding of NFS affected foals.