ATP2A2 SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation
| Autor: | Linek, Monika, Doelle, Maren, Leeb, Tosso, Bauer, Anina, Leuthard, Fabienne, Henkel, Jan, Bannasch, Danika, Jagannathan, Vidya, Welle, Monika M. |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Keratinocytes
Heterozygote skin lcsh:QH426-470 Canis lupus familiaris precision medicine 610 Medicine & health Calcium-Transporting ATPases Haploinsufficiency Article Sarcoplasmic Reticulum Calcium-Transporting ATPases Dogs Genetics Animals Humans 2.1 Biological and endogenous factors Dog Diseases Aetiology acantholysis calcium 630 Agriculture Benign Familial animal model dermatology lcsh:Genetics veterinary medicine dog 590 Animals (Zoology) 570 Life sciences biology Female Epidermis desmosome Darier Disease Ear Canal Pemphigus |
| Zdroj: | Genes Volume 11 Issue 5 Genes, Vol 11, Iss 481, p 481 (2020) Genes, vol 11, iss 5 Linek, Monika; Doelle, Maren; Leeb, Tosso; Bauer, Anina; Leuthard, Fabienne; Henkel, Jan; Bannasch, Danika; Jagannathan, Vidya; Welle, Monika M. (2020). ATP2A2 SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation. Genes, 11(5) MDPI, Molecular Diversity Preservation International 10.3390/genes11050481 |
| ISSN: | 2073-4425 |
| DOI: | 10.3390/genes11050481 |
| Popis: | A 4-month-old female Irish Terrier presented with a well demarcated ulcerative and crusting lesion in the right ear canal. Histological analysis revealed epidermal hyperplasia with severe acantholysis affecting all suprabasal layers of the epidermis, which prompted a presumptive diagnosis of canine Darier disease. The lesion was successfully treated by repeated laser ablation of the affected epidermis. Over the course of three years, the dog additionally developed three dermal nodules of up to 4 cm in diameter that were excised and healed without complications. Histology of the excised tissue revealed multiple infundibular cysts extending from the upper dermis to the subcutis. The cysts were lined by squamous epithelium, which presented with abundant acantholysis of suprabasal keratinocytes. Infundibular cysts represent a novel finding not previously reported in Darier patients. Whole genome sequencing of the affected dog was performed, and the 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. As Darier disease in humans is caused by haploinsufficiency of ATP2A2, our genetic findings are in agreement with the clinical and histopathological data and support the diagnosis of canine Darier disease. |
| Databáze: | OpenAIRE |
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