A nonsense variant in the KRT14 gene in a domestic shorthair cat with epidermolysis bullosa simplex

Abstract

Summary Epidermolysis bullosa simplex (EBS) is a hereditary blistering disease affecting the skin and mucous membranes. It has been reported in humans, cattle, buffaloes and dogs, but so far not in cats. In humans, EBS is most frequently caused by variants in the KRT5 or KRT14 genes. Here, we report a case of feline epidermolysis bullosa simplex and describe the causative genetic variant. An 11‐month‐old male domestic shorthair cat presented with a history of sloughed paw pads and ulcerations in the oral cavity and inner aspect of the pinnae, starting a few weeks after birth. Clinical and histopathological findings suggested a congenital blistering disease with a split formation within the basal cell layer of the epidermis and oral mucous epithelium. The genetic investigation revealed a homozygous nonsense variant in the KRT14 gene (c.979C>T, p.Gln327*). Immunohistochemistry showed a complete absence of keratin 14 staining in all epithelia present in the biopsy. To the best of our knowledge, this is the first report of feline EBS, and the first report of a spontaneous pathogenic KRT14 variant in a non‐human species. The homozygous genotype in the affected cat suggests an autosomal recessive mode of inheritance.

Independent COL17A1 Variants in Cats with Junctional Epidermolysis Bullosa

“…EB is a rare disease also in the feline species, with few cases reported at the clinicopathological level. Previously reported cases were characterized by onychomadesis and localized or generalized skin and oral ulcerations, resulting in either mild or severe phenotypes, as seen in our cases [9,13,19,42]. A KRT14 variant was identified in a single cat with EBS [19].…”

“…Previously reported cases were characterized by onychomadesis and localized or generalized skin and oral ulcerations, resulting in either mild or severe phenotypes, as seen in our cases [9,13,19,42]. A KRT14 variant was identified in a single cat with EBS [19]. In another study involving two cats diagnosed with JEB, LAMC2 and LAMB3 were identified as possible candidate genes by indirect immunofluorescence, but the underlying genetics was not reported [13].…”

“…In contrast to humans, where more than 1000 variants in at least 16 genes have been associated with EB [1], molecular studies are rarely reported in domestic animals. EBS was associated with variants in PLEC in a litter of dogs [15], KRT5 in cattle [16,17] and a dog [18], and KRT14 in a cat [19]. DEB was associated with variants in COL7A1 in cattle [20] and dogs [21].…”

KRT5 in‐frame deletion in a family of German Shepherd dogs with split paw pad disease resembling localized epidermolysis bullosa simplex in human patients

“…The resulting keratin filament network is connected to hemidesmosomes, which attach the basal keratinocytes to the underlying basement membrane (Walko et al., 2015). Genetic variants in KRT5 and KRT14 are known to represent the most frequent cause of epidermolysis bullosa simplex (EBS) in humans and animals alike (Bergson et al., 2023; Dettwiler et al., 2020; Kiener et al., 2022; Lane et al., 1992). EBS is the most widespread type of epidermolysis bullosa (Has et al., 2020).…”