Subject(s)
Frameshift Mutation , Heterozygote , Ichthyosis , Animals , Ichthyosis/genetics , Ichthyosis/veterinary , Dog Diseases/genetics , Dogs/geneticsABSTRACT
In a litter of Turkish Van cats, three out of six kittens developed severe signs of skin disease, diarrhea, and systemic signs of stunted growth at 6 weeks of age. Massive secondary infections of the skin lesions evolved. Histopathological examinations showed a mild to moderate hyperplastic epidermis, covered by a thick layer of laminar to compact, mostly parakeratotic keratin. The dermis was infiltrated with moderate amounts of lymphocytes and plasma cells. Due to the severity of the clinical signs, one affected kitten died and the other two had to be euthanized. We sequenced the genome of one affected kitten and compared the data to 54 control genomes. A search for private variants in the two candidate genes for the observed phenotype, MKLN1 and SLC39A4, revealed a single protein-changing variant, SLC39A4:c.1057G>C or p.Gly353Arg. The solute carrier family 39 member 4 gene (SLC39A4) encodes an intestinal zinc transporter required for the uptake of dietary zinc. The variant is predicted to change a highly conserved glycine residue within the first transmembrane domain, which most likely leads to a loss of function. The genotypes of the index family showed the expected co-segregation with the phenotype and the mutant allele was absent from 173 unrelated control cats. Together with the knowledge on the effects of SLC39A4 variants in other species, these data suggest SLC39A4:c.1057G>C as candidate causative genetic variant for the phenotype in the investigated kittens. In line with the human phenotype, we propose to designate this disease acrodermatitis enteropathica (AE).
Subject(s)
Acrodermatitis/veterinary , Cation Transport Proteins/genetics , Cats/genetics , Zinc/deficiency , Acrodermatitis/diagnosis , Acrodermatitis/genetics , Acrodermatitis/pathology , Animals , Biopsy , DNA Mutational Analysis , Female , Male , Mutation, Missense , Pedigree , Skin/pathology , Whole Genome SequencingABSTRACT
BACKGROUND: In the Griffon breeds (GB) nasal hyperkeratosis is common and develops already in early adulthood. Breed-related features and prevalence have not previously been documented. HYPOTHESIS/OBJECTIVES: To describe clinical and histopathological features of nasal hyperkeratosis in GB and to document the prevalence. MATERIALS AND METHODS: Seven GB dogs with nasal hyperkeratosis were examined. Three histopathological samples were analysed. Owners of 107 GB and 493 control dogs completed a questionnaire distributed via social media. RESULTS: Typical features of nasal hyperkeratosis in GB included varying degrees of dry, firm, excessive proliferation of keratin, affecting the dorsal or dorsolateral aspect of the planum nasale. Histopathology was characterized by severe, lamellar orthokeratotic and focal parakeratotic hyperkeratosis and multiple small serum lakes. Thirty-four of 107 GB dogs (31.8%) and 65 of 493 (13.2%) control dogs had varying degree of nasal hyperkeratosis. No sex predisposition was noted. Median age of onset was 3 years for GB, similar to brachycephalic control dogs whereas non-brachycephalic control dogs had a significantly later age of onset (p = 0.0053). CONCLUSIONS AND CLINICAL IMPORTANCE: Idiopathic nasal hyperkeratosis is very common in GB dogs and other brachycephalic breeds with nearly one third being affected, often already a young age.
