In ichthyosis, desquamation of corneocytes is impaired, resulting in retained large squames and thus severe hyperkeratosis, as well as loss of skin elasticity and an abnormal barrier function. They are linked by the common finding of a thickened stratum corneum resulting in localized or generalized scaling. Ichthyoses encompass a heterogeneous group of congenital disorders characterized by an abnormal terminal keratinocyte differentiation. The findings were added to the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002243-9913). The results of our study enable genetic testing to avoid the unintentional occurrence of further affected cattle. To the best of our knowledge, this study is also the first report of a DSP-related syndromic form of congenital ichthyosis in domestic animals. This study represents the first report of combined lesions compatible with congenital ichthyosis, alopecia, acantholysis of the tongue and corneal defects associated with a DSP missense variant as the most likely underlying cause. The mutant allele was absent in more than 4800 controls from various other cattle breeds. Further genotyping of 257 Scottish Highland animals from Switzerland revealed an estimated allele frequency of 1.2%. Sanger sequencing confirmed the variant was homozygous in the affected calf and heterozygous in both parents. The variant is predicted to change a highly conserved residue in the C-terminal plakin domain of the desmoplakin protein, which represents a main intracellular component of desmosomes, important intercellular adhesion molecules in various tissues including epidermis. A search for private variants in known candidate genes for skin phenotypes including genes related with erosive and hyperkeratotic lesions revealed a single homozygous protein-changing variant, DSP: c.6893 C>A, or p.Ala2298Asp. Whole-genome sequencing of the affected calf and comparison of the data with control genomes was performed. Post-mortem examination revealed deep fissures in the diffusely thickened tongue and histopathological findings in the skin confirmed the clinical diagnosis. Additionally, conjunctivitis and ulceration of the cornea were noted. The clinical phenotype included diffuse alopecia and a markedly lichenified skin covered with large and excessive scales. ResultsĪ 2-weeks-old purebred Scottish Highland calf was referred because of a syndrome resembling congenital ichthyosis. Two rare bovine forms are reported, the severe harlequin ichthyosis and the less severe congenital ichthyosis, both characterized by a severe orthokeratotic lamellar hyperkeratosis. Ichthyosis describes a localized or generalized hereditary cornification disorder caused by an impaired terminal keratinocyte differentiation resulting in excessive stratum corneum with the formation of more or less adherent scales.
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