OMIA 002265-9615 : Darier disease in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 124200

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2020

Molecular basis: Linek et al. (2020): "Whole genome sequencing of the affected dog was performed, and the [comparative] functional candidate genes for Darier disease (ATP2A2) and Hailey-Hailey disease (ATP2C1) were investigated. The analysis revealed a heterozygous SINE insertion into the ATP2A2 gene, at the end of intron 14, close to the boundary of exon 15. Analysis of the ATP2A2 mRNA from skin of the affected dog demonstrated a splicing defect and marked allelic imbalance, suggesting nonsense-mediated decay of the resulting aberrant transcripts."

Clinical features: Linek et al. (2020): "clinical, histological, immunohistological, and ultrastructural findings in a male English Setter and two of its female offspring were initially reported as Hailey-Hailey disease [Shanley et al., 1993; Sueki et al., 1997]. A subsequent study found depletion of the ATP2A2-gated stores in cultured keratinocytes from one of these dogs and suggested that these dogs had Darier disease and not Hailey-Hailey disease as previously reported [Müller et al., 2006]."

Breed: Irish Terrier.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ATP2A2 ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 Canis lupus familiaris 26 NC_051830.1 (8406466..8467508) ATP2A2 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Irish Terrier Darier disease ATP2A2 insertion, gross (>20) CanFam3.1 26 p.(Thr700Valfs*6) Linek et al. (2020): "a heterozygous SINE insertion [~205bp] into the ATP2A2 gene, at the end of intron 14, close to the boundary of exon 15", giving rise to NP_001003214.1:p.(Thr700Valfs*6) 2020 32354065

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.
2020 Linek, M., Doelle, M., Leeb, T., Bauer, A., Leuthard, F., Henkel, J., Bannasch, D., Jagannathan, V., Welle, M.M. :
ATP2A2 SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation. Genes (Basel) 11:, 2020. Pubmed reference: 32354065. DOI: 10.3390/genes11050481.
2006 Müller, E.J., Caldelari, R., Kolly, C., Williamson, L., Baumann, D., Richard, G., Jensen, P., Girling, P., Delprincipe, F., Wyder, M., Balmer, V., Suter, M.M. :
Consequences of depleted SERCA2-gated calcium stores in the skin. J Invest Dermatol 126:721-31, 2006. Pubmed reference: 16397524. DOI: 10.1038/sj.jid.5700091.
1997 Sueki, H., Shanley, K., Goldschmidt, M.H., Lazarus, G.S., Murphy, G.F. :
Dominantly inherited epidermal acantholysis in dogs, simulating human benign familial chronic pemphigus (Hailey-Hailey disease) British Journal of Dermatology 136:190-196, 1997. Pubmed reference: 9068730.
1993 Shanley, K.J., Goldschmidt, M.H., Sueki, H., Lazarus, G., George, M. :
Canine Benign Familial Chronic Pemphigus. Advances in Veterinary Dermatology 2:353–365, 1993.

Edit History


  • Created by Frank Nicholas on 14 May 2020
  • Changed by Frank Nicholas on 14 May 2020