OMIA:001415-9615 : Hyperkeratosis, epidermolytic in Canis lupus familiaris (dog) |
In other species: walrus
Categories: Integument (skin) phene
Links to possible relevant human trait(s) and/or gene(s) in OMIM: 113800 (trait) , 609165 (trait) , 607602 (trait) , 148080 (gene)
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal
Disease-related: yes
Key variant known: yes
Year key variant first reported: 2005
Species-specific name: Epidermolytic hyperkeratosis; epidermolytic ichthyosis
Species-specific description: This disorder is a form of ichthyosis.
Inheritance: Mode of inheritance is described as recessive in Norfolk Terriers and as likely dominant in a single Chihuahua (Credille et al., 2005; Kiener et al., 2023).
Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Credille et al. (2005) documented the molecular basis of this disorder in a family of Norfolk terrier dogs: "Affected dogs were homozygous for a single base GT>TT change in the consensus donor splice site of intron 5 in [the gene for keratin 10] KRT10. . . . . The mutation caused activation of at least three cryptic or alternative splice sites. Use of the cryptic sites resulted in transcripts containing premature termination codons. One transcript could result in shortening of the proximal portion of the 2B domain before the stutter region." Kiener et al. (2023) investigated an affected Chihuahua. Analysis of whole genome sequencing data identified a likely de-novo heterozygous missense variant (Chr9:21814695G>A, XM_038547368.1:c.437G>A, XP_038403296.1:p.(Arg146His)) in the KRT10 candidate gene. "Heterozygous variants affecting human Arg156, homologous to canine Arg146, have been described in several human patients with epidermolytic hyperkeratosis ... ."
Clinical features: "Adult [Norfolk Terrier] dogs with the disease had generalized, pigmented hyperkeratosis with epidermal fragility." (Credille et al., 2005) Kiener et al. (2023) investigated an "11-month-old male Chihuahua ... with severe skin lesions gradually progressing from 5 months of age. Clinical examination revealed severe, multifocal hyperkeratosis, mainly affecting paw pads, axillas and the skin around the anus, lips and eyes ... ."
Pathology: "Light microscopic examination defined epidermolysis with hyperkeratosis; ultrastructural changes included a decrease in tonofilaments and abnormal filament aggregation in upper spinous and granular layer keratinocytes." (Credille et al., 2005) Kiener et al. (2023) reported "marked epidermal hyperplasia and orthokeratotic hyperkeratosis with hypergranulosis, forming papillary projections on the skin surface" in skin biopsies of an affected Chihuahua.
Breeds:
Chihuahua (Dog) (VBO_0200338),
Labrador Retriever (Dog) (VBO_0200800),
Norfolk Terrier (Dog) (VBO_0200945),
Rhodesian Ridgeback (Dog) (VBO_0201135).
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:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| KRT10 | keratin 10, type I | Canis lupus familiaris | 9 | NC_051813.1 (22656504..22661353) | KRT10 | Homologene, Ensembl , NCBI gene |
Variants
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
| OMIA Variant ID | Breed(s) | Variant Phenotype | Gene | Allele | Type of Variant | Source of Genetic Variant | Reference Sequence | Chr. | g. or m. | c. or n. | p. | Verbal Description | EVA ID | Year Published | PubMed ID(s) | Acknowledgements |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 364 | Norfolk Terrier (Dog) | Hyperkeratosis, epidermolytic | KRT10 | splicing | Naturally occurring variant | CanFam3.1 | 9 | g.21866234G>T | c.1125+1G>T | XM_038676544.1; XP_038532472.1; experimentally confirmed splice defect; a single base GT>TT change in the consensus 5'-splice site of intron 5 | 2005 | 16029326 | ||||
| 1579 | Chihuahua (Dog) | Ichthyosis, epidermolytic | KRT10 | missense | Naturally occurring variant | UU_Cfam_GSD_1.0 | 9 | g.21814695G>A | c.437G>A | p.(R146H) | XM_038547368.1; XP_038403296 | 2023 | 37332248 |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:001415-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70
References
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
| 2023 | Kiener, S., Åhman, S., Jagannathan, V., Soto, S., Leeb, T. : |
| Heterozygous KRT10 missense variant in a Chihuahua with severe epidermolytic ichthyosis. Anim Genet 54:652-654, 2023. Pubmed reference: 37332248. DOI: 10.1111/age.13341. | |
| Meadows, J.R.S., Kidd, J.M., Wang, G.D., Parker, H.G., Schall, P.Z., Bianchi, M., Christmas, M.J., Bougiouri, K., Buckley, R.M., Hitte, C., Nguyen, A.K., Wang, C., Jagannathan, V., Niskanen, J.E., Frantz, L.A.F., Arumilli, M., Hundi, S., Lindblad-Toh, K., Ginja, C., Agustina, K.K., André, C., Boyko, A.R., Davis, B.W., Drögemüller, M., Feng, X.Y., Gkagkavouzis, K., Iliopoulos, G., Harris, A.C., Hytönen, M.K., Kalthoff, D.C., Liu, Y.H., Lymberakis, P., Poulakakis, N., Pires, A.E., Racimo, F., Ramos-Almodovar, F., Savolainen, P., Venetsani, S., Tammen, I., Triantafyllidis, A., vonHoldt, B., Wayne, R.K., Larson, G., Nicholas, F.W., Lohi, H., Leeb, T., Zhang, Y.P., Ostrander, E.A. : | |
| Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture. Genome Biol 24:187, 2023. Pubmed reference: 37582787. DOI: 10.1186/s13059-023-03023-7. | |
| 2022 | Marín-García, P.J., Llobat, L. : |
| Inheritance of monogenic hereditary skin disease and related canine breeds. Vet Sci 9:433, 2022. Pubmed reference: 36006348. DOI: 10.3390/vetsci9080433. | |
| 2021 | Malinovská, Z., Čonková, E. : |
| Ichthyosis in dogs—Congenital dermatologic disorder. Folia Veterinaria 65:22-29, 2021. DOI: doi.org/10.2478/fv-2021-0024. | |
| 2005 | Barnhart, KF., Credille, KM., Ambrus, A., Dunstan, RW. : |
| Preservation of phenotype in an organotypic cell culture model of a recessive keratinization defect of Norfolk terrier dogs. Exp Dermatol 14:481-90, 2005. Pubmed reference: 15946235. DOI: 10.1111/j.0906-6705.2005.00306.x. | |
| Credille, KM., Barnhart, KF., Minor, JS., Dunstan, RW. : | |
| Mild recessive epidermolytic hyperkeratosis associated with a novel keratin 10 donor splice-site mutation in a family of Norfolk terrier dogs. Br J Dermatol 153:51-8, 2005. Pubmed reference: 16029326. DOI: 10.1111/j.1365-2133.2005.06735.x. | |
| 2004 | Barnhart, KF., Credille, KM., Ambrus, A., Dunstan, RW. : |
| A heritable keratinization defect of the superficial epidermis in Norfolk terriers. J Comp Pathol 130:246-54, 2004. Pubmed reference: 15053927. DOI: 10.1016/j.jcpa.2003.11.003. | |
| 2000 | Mecklenburg, L., Hetzel, U., Ueberschär, S. : |
| Epidermolytic ichthyosis in a dog: clinical, histopathological, immunohistochemical and ultrastructural findings. J Comp Pathol 122:307-11, 2000. Pubmed reference: 10805985. DOI: 10.1053/jcpa.1999.0371. |
Edit History
- Created by Frank Nicholas on 05 Oct 2005
- Changed by Frank Nicholas on 28 Sep 2011
- Changed by Frank Nicholas on 12 Dec 2011
- Changed by Frank Nicholas on 16 Jan 2012
- Changed by Frank Nicholas on 27 Jan 2012
- Changed by Frank Nicholas on 21 Oct 2012
- Changed by Imke Tammen2 on 20 Jun 2023
- Changed by Imke Tammen2 on 12 Jun 2024