A variant in the gene in a dog with ichthyosis

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The skin undergoes a constant process of self-renewing and keratinocytes migrate from the basal layer of the epidermis to the uppermost layer, the stratum corneum, as they differentiate. A defect in the differentiation of keratinocytes can lead to cornification disorders such as ichthyosis. The most common form of this disorder in humans is ichthyosis vulgaris caused by variants in the filaggrin gene. Filaggrin is required for bundling intermediate filaments resulting in the flattening of keratinocytes. Filaggrin is produced from profilaggrin and the processing steps involve several enzymes including proteases. In the present study, we sequenced the genome of a dog with a novel form of ichthyosis. By comparing this sequence to 288 control genomes, we identified a private missense variant in the ASPRV1 gene encoding the retroviral-like aspartic protease 1, also known as SASPase, which is involved in the processing of profilaggrin. The variant was due to a de novo mutation event, which is consistent with the patient being an isolated single case of a novel form of ichthyosis. Filaggrin protein expression was altered in the skin of the affected dog. Thus, our results strongly suggest that genetic variants in ASPRV1 can cause ichthyosis by altering filaggrin processing.

Vyšlo v časopise: A variant in the gene in a dog with ichthyosis. PLoS Genet 13(3): e32767. doi:10.1371/journal.pgen.1006651
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1006651

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