Skin barrier, phenotypic and genotypic characterisation of autosomal recessive ichthyosis in TGM1‐deficient Jack Russell Terriers and response to topical ceramide

Abstract

AbstractBackgroundAutosomal recessive ichthyosis leads to structural or biochemical changes that impair skin barrier function.Hypothesis/ObjectivesTo assess (1) the phenotype and genotype in a litter of Jack Russell Terriers with autosomal recessive congenital ichthyosis (ARCI), and (2) the defective skin barrier and determine if a topical ceramide can modulate the barrier.AnimalsA healthy dam and litter of Jack Russell Terrier puppies (healthy male, affected male and female), one affected adult Jack Russell Terrier and one unrelated healthy Jack Russell Terrier.Materials and MethodsA severe cornification defect was identified via examination of affected puppies. As the phenotype worsened, the affected puppies received a topical application of ω‐0‐acylceramide for 10 days. Before humane euthanasia, the skin barrier was evaluated via transepidermal water loss (TEWL), corneometry and pH in affected dogs. Genomic testing was performed, and skin samples were analysed by light and electron microscopy.ResultsAffected puppies were homozygous for the 1980 bp LINE‐1 insertion in the TGM1 (transglutaminase 1) gene; the unaffected littermate and the dam were heterozygous carriers. ARCI puppies were underweight and had a severe hyperkeratotic phenotype that impaired mobility. TEWL was markedly higher in affected dogs. The cutaneous pH of affected puppies was higher than the normal littermate. Treatment of the skin with ω‐0‐acylceramide normalised the pH to match the littermate and decreased TEWL. Electron microscopy revealed marked attenuation of the cornified envelope.Conclusions and Clinical RelevanceDogs with TGM1‐deficient ARCI have an impaired skin barrier. Topical therapy can partially repair the barrier defect.