Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Dec;53(6):892-896.
doi: 10.1111/age.13257. Epub 2022 Aug 25.

KRT5 missense variant in a Cardigan Welsh Corgi with epidermolysis bullosa simplex

Sarah Kiener  1   2 , Elizabeth A Mauldin  3 , Vidhya Jagannathan  1   2 , Margret L Casal  3 , Tosso Leeb  1   2
Affiliations

KRT5 missense variant in a Cardigan Welsh Corgi with epidermolysis bullosa simplex

Sarah Kiener et al. Anim Genet. 2022 Dec.

Abstract

Epidermolysis bullosa (EB) is a group of blistering disorders that includes several subtypes, classified according to their level of cleavage. Typical clinical signs are blisters and erosions resulting from minimal trauma. The disease has been described in many mammalian species and pathogenic variants in at least 18 different genes have been identified. In the present study, we investigated a Cardigan Welsh Corgi with congenital clinical signs consistent with epidermolysis bullosa. The puppy had blisters and erosions on the paw pads, and the oral mucosa. Histologic examination demonstrated the typical clefting between the dermis and epidermis and confirmed the clinical suspicion. We obtained whole genome sequencing data from the affected puppy and searched for variants in candidate genes known to cause EB. This revealed a heterozygous missense variant, KRT5:p.(E476K), affecting the highly conserved KLLEGE motif of keratin 5. The mutant allele in the affected puppy arose owing to a de novo mutation event as it was absent from both unaffected parents. Knowledge of the functional impact of KRT5 variants in other species together with the demonstration of the de novo mutation event establishes KRT5:p.(E476K) as causative variant for the observed EBS.

Keywords: Canis lupus familiaris; animal model; dermatology; dog; genodermatosis; precision medicine; skin; veterinary medicine.

PubMed Disclaimer

Conflict of interest statement

The author declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Phenotype of the Cardigan Welsh Corgi affected with epidermolysis bullosa. (a) Underweight 12‐day‐old puppy. (b) Extensive ulcers in the oral cavity. Note that the epidermis sloughs with gentle pressure on the perioral skin. (c) Numerous vesicles on the paw pads. (d) Broad subepidermal vesicle with remnants of basal keratinocytes at the marginal base of the blister (thin arrows in black circle). H&E 10×.
FIGURE 2
FIGURE 2
Details of the identified variant in KRT5. (a) Electropherograms showing the KRT5:C.1426G>a missense variant. The variable position is indicated with an arrow and the amino acid translations are shown. (b) Pedigree of the family of the affected dog. Squares represent males and circles represent females. The filled symbol indicates the affected dog. The genotypes for each animal at the position of the identified KRT5 variant are given. (c) Multiple‐species alignment of the KRT5 protein in the region of the p.E476K variant. The variant affects the first glutamate residue of the highly conserved KLLEGE motif (underlined).
See this image and copyright information in PMC

References

    1. Arin, M.J. (2009) The molecular basis of human keratin disorders. Human Genetics, 125(4), 355–373. 10.1007/s00439-009-0646-5 - DOI - PubMed
    1. Baldeschi, C. , Gache, Y. , Rattenholl, A. , Bouille, P. , Danos, O. , Ortonne, J.‐P. et al. (2003) Genetic correction of canine dystrophic epidermolysis bullosa mediated by retroviral vectors. Human Molecular Genetics, 12(15), 1897–1905. 10.1093/hmg/ddg200 - DOI - PubMed
    1. Capt, A. , Spirito, F. , Guaguere, E. , Spadafora, A. , Ortonne, J.‐P. & Meneguzzi, G. (2005) Inherited junctional epidermolysis bullosa in the German pointer: establishment of a large animal model. Journal of Investigative Dermatology, 124(3), 530–535. 10.1111/j.0022-202X.2004.23584.x - DOI - PubMed
    1. Fine, J.‐D. , Eady, R.A.J. , Bauer, E.A. , Bauer, J.W. , Bruckner‐Tuderman, L. , Heagerty, A. et al. (2008) The classification of inherited epidermolysis bullosa (EB): report of the third international consensus meeting on diagnosis and classification of EB. Journal of the American Academy of Dermatology, 58(6), 931–950. 10.1016/j.jaad.2008.02.004 - DOI - PubMed
    1. Ford, C.A. , Stanfield, A.M. , Spelman, R.J. , Smits, B. , Ankersmidt‐Udy, A.E.L. , Cottier, K. et al. (2005) A mutation in bovine keratin 5 causing epidermolysis bullosa simplex, transmitted by a mosaic sire. Journal of Investigative Dermatology, 124(6), 1170–1176. 10.1111/j.0022-202X.2005.23610.x - DOI - PubMed