Categories: Integument (skin) phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 146750 (trait) , 611765 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2017

Molecular basis: Bauer et al. (2017): "Comparing the genome sequence of the affected dog with 288 genomes from genetically diverse non-affected dogs we identified a private heterozygous variant in the ASPRV1 gene encoding "aspartic peptidase, retroviral-like 1", which is also known as skin aspartic protease (SASPase). The variant [omia.variant:111] was absent in both parents and therefore due to a de novo mutation event. It was a missense variant, c.1052T>C, affecting a conserved residue close to an autoprocessing cleavage site, p.(Leu351Pro). " The authors showed altered filaggrin processing in the affected dog with the ASPRV1 variant. Filaggrin is important for skin integrity and variants in the filaggrin gene lead to ichthyosis vulgaris in humans.
Kiener et al. (2024) identified a second candidate causative variant in ASPRV1 [omia.variant:1673] in a Pembroke Welsh Corgi with clinically and histopathologically diagnosed ichthyosis:  NC_049231.1:69888722_69888723del. The variant is a 2-bp deletion introducing a frameshift and predicted to result in an extended protein, p.(Leu199Argfs*342).

Clinical features: Bauer et al. (2017) "describe a novel non-epidermolytic form of ichthyosis in a German Shepherd. In this breed, until now, no ichthyosis cases have been reported in the scientific literature. . . . Dermatological examination revealed generalized hypotrichosis and focal areas of alopecia with generalized severe exfoliation of greyish scales and mild erythema. Comedones were seen on the ventral abdomen and in the perivulvar area."

Pathology: Bauer et al. (2017): "Histopathological analysis of four skin biopsies from different body regions revealed a severe laminar to compact orthokeratotic hyperkeratosis extending into the follicular infundibula in all biopsies. The keratin layers were multifocally exfoliating as large scales. The underlying epidermis was mildly hyperplastic. In the biopsy from the inguinal region, the infundibula of the hair follicles were moderately dilated. The histological findings were consistent with a cornification disorder and an inherited non-epidermolytic ichthyosis as possible cause."

Breeds: German Shepherd Dog (Dog) (VBO_0200577), Pembroke Welsh Corgi (Dog) (VBO_0200995).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: