Next Article in Journal
Study of Quantitative Trait Loci (QTLs) Associated with Allelopathic Trait in Rice
Next Article in Special Issue
ATP2A2 SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation
Previous Article in Journal
Identification of Age-Specific and Common Key Regulatory Mechanisms Governing Eggshell Strength in Chicken Using Random Forests
Previous Article in Special Issue
Whole Genome Sequencing Indicates Heterogeneity of Hyperostotic Disorders in Dogs
Article

A DSG1 Frameshift Variant in a Rottweiler Dog with Footpad Hyperkeratosis

1
School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2
Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland
3
Dermfocus, University of Bern, 3001 Bern, Switzerland
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work (shared first authors).
These authors contributed equally to this work (shared senior authors).
Genes 2020, 11(4), 469; https://doi.org/10.3390/genes11040469
Received: 1 April 2020 / Revised: 23 April 2020 / Accepted: 23 April 2020 / Published: 24 April 2020
(This article belongs to the Special Issue Molecular Basis of Inherited Diseases in Companion Animals)
A single male Rottweiler dog with severe footpad hyperkeratosis starting at an age of eight weeks was investigated. The hyperkeratosis was initially restricted to the footpads. The footpad lesions caused severe discomfort to the dog and had to be trimmed under anesthesia every 8–10 weeks. Histologically, the epidermis showed papillated villous projections of dense keratin in the stratum corneum. Starting at eight months of age, the patient additionally developed signs consistent with atopic dermatitis and recurrent bacterial skin and ear infections. Crusted hyperkeratotic plaques developed at sites of infection. We sequenced the genome of the affected dog and compared the data to 655 control genomes. A search for variants in 32 candidate genes associated with human palmoplantar keratoderma (PPK) revealed a single private protein-changing variant in the affected dog. This was located in the DSG1 gene encoding desmoglein 1. Heterozygous monoallelic DSG1 variants have been reported in human patients with striate palmoplantar keratoderma I (SPPK1), while biallelic DSG1 loss of function variants in humans lead to a more pronounced condition termed severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome. The identified canine variant, DSG1:c.2541_2545delGGGCT, leads to a frameshift and truncates about 20% of the coding sequence. The affected dog was homozygous for the mutant allele. The comparative data on desmoglein 1 function in humans suggest that the identified DSG1 variant may have caused the footpad hyperkeratosis and predisposition for allergies and skin infections in the affected dog. View Full-Text
Keywords: Canis lupus familiaris; whole-genome sequence; animal model; genodermatosis; skin; dermatology; keratinocyte; SAM syndrome; precision medicine Canis lupus familiaris; whole-genome sequence; animal model; genodermatosis; skin; dermatology; keratinocyte; SAM syndrome; precision medicine
Show Figures

Figure 1

MDPI and ACS Style

Backel, K.A.; Kiener, S.; Jagannathan, V.; Casal, M.L.; Leeb, T.; Mauldin, E.A. A DSG1 Frameshift Variant in a Rottweiler Dog with Footpad Hyperkeratosis. Genes 2020, 11, 469. https://doi.org/10.3390/genes11040469

AMA Style

Backel KA, Kiener S, Jagannathan V, Casal ML, Leeb T, Mauldin EA. A DSG1 Frameshift Variant in a Rottweiler Dog with Footpad Hyperkeratosis. Genes. 2020; 11(4):469. https://doi.org/10.3390/genes11040469

Chicago/Turabian Style

Backel, Katherine A., Sarah Kiener, Vidhya Jagannathan, Margret L. Casal, Tosso Leeb, and Elizabeth A. Mauldin. 2020. "A DSG1 Frameshift Variant in a Rottweiler Dog with Footpad Hyperkeratosis" Genes 11, no. 4: 469. https://doi.org/10.3390/genes11040469

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop