SDR9C7 missense variant in a Chihuahua with non‐epidermolytic ichthyosis

Abstract

Ichthyoses represent a heterogeneous group of cornification disorders that are associated with skin barrier defects. We investigated a 9-monthold Chihuahua showing excessive scale formation. Clinical and histopathological examinations revealed non-epidermolytic ichthyosis and a genetic defect was suspected. We therefore sequenced the genome of the affected dog and compared the data with 564 genetically diverse control genomes. Filtering for private variants identified a homozygous missense variant in SDR9C7, c.454C>T or p.(Arg152Trp). SDR9C7 is a known candidate gene for ichthyosis in humans and encodes the short-chain dehydrogenase/ reductase family 9C member 7. The enzyme is involved in the production of a functional corneocyte lipid envelope (CLE), a crucial component of the epidermal barrier. Pathogenic variants in SDR9C7 have been described in human patients with autosomal recessive ichthyosis. We assume that the identified missense variant in the affected Chihuahua of this study impairs the normal enzymatic activity of SDR9C7 and thus prevents the formation of a functioning CLE, resulting in a defective skin barrier. To the best of our knowledge, this is the first report of a spontaneous SDR9C7 variant in domestic animals.

Heterozygous ASPRV1 frameshift variant in a Pembroke Welsh Corgi with ichthyosis

“…lysis of keratinocytes (Mauldin, 2013). In dogs, several breed-specific ichthyoses have been described, and, to date, causal variants in nine different genes have been identified (Affolter et al, 2022;Bauer et al, 2017;Briand et al, 2019;Casal et al, 2017;Credille et al, 2005Credille et al, , 2009Grall et al, 2012;Kiener et al, 2022;Kiener, Åhman, et al, 2023;Kiener, Castilla, et al, 2023;Metzger et al, 2015). These genes are mainly involved in the biosynthesis, metabolism, and transport of lipids required for skin barrier function or the intracellular protein network responsible for the integrity of skin structure (Gutiérrez-Cerrajero et al, 2023).…”