<i>ATP2A2</i> SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation
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...
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MDPI AG
2020-04-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/11/5/481 |
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| author | Monika Linek Maren Doelle Tosso Leeb Anina Bauer Fabienne Leuthard Jan Henkel Danika Bannasch Vidhya Jagannathan Monika M. Welle |
| author_facet | Monika Linek Maren Doelle Tosso Leeb Anina Bauer Fabienne Leuthard Jan Henkel Danika Bannasch Vidhya Jagannathan Monika M. Welle |
| author_sort | Monika Linek |
| collection | DOAJ |
| description | 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 (<i>ATP2A2</i>) and Hailey-Hailey disease (<i>ATP2C1</i>) were investigated. The analysis revealed a heterozygous SINE insertion into the <i>ATP2A2</i> gene, at the end of intron 14, close to the boundary of exon 15. Analysis of the <i>ATP2A2</i> 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 <i>ATP2A2</i>, our genetic findings are in agreement with the clinical and histopathological data and support the diagnosis of canine Darier disease. |
| first_indexed | 2024-03-10T20:10:26Z |
| format | Article |
| id | doaj.art-60c2ba8e93bd4ef2a7e93385337cbf68 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T20:10:26Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-60c2ba8e93bd4ef2a7e93385337cbf682023-11-19T22:57:00ZengMDPI AGGenes2073-44252020-04-0111548110.3390/genes11050481<i>ATP2A2</i> SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst FormationMonika Linek0Maren Doelle1Tosso Leeb2Anina Bauer3Fabienne Leuthard4Jan Henkel5Danika Bannasch6Vidhya Jagannathan7Monika M. Welle8AniCura Tierärztliche Spezialisten, 22043 Hamburg, GermanyAniCura Tierärztliche Spezialisten, 22043 Hamburg, GermanyInstitute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, SwitzerlandInstitute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, SwitzerlandInstitute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, SwitzerlandInstitute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, SwitzerlandInstitute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, SwitzerlandInstitute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, SwitzerlandDermfocus, University of Bern, 3001 Bern, SwitzerlandA 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 (<i>ATP2A2</i>) and Hailey-Hailey disease (<i>ATP2C1</i>) were investigated. The analysis revealed a heterozygous SINE insertion into the <i>ATP2A2</i> gene, at the end of intron 14, close to the boundary of exon 15. Analysis of the <i>ATP2A2</i> 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 <i>ATP2A2</i>, our genetic findings are in agreement with the clinical and histopathological data and support the diagnosis of canine Darier disease.https://www.mdpi.com/2073-4425/11/5/481<i>Canis lupus familiaris</i>dogdermatologyskindesmosomeacantholysis |
| spellingShingle | Monika Linek Maren Doelle Tosso Leeb Anina Bauer Fabienne Leuthard Jan Henkel Danika Bannasch Vidhya Jagannathan Monika M. Welle <i>ATP2A2</i> SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation Genes <i>Canis lupus familiaris</i> dog dermatology skin desmosome acantholysis |
| title | <i>ATP2A2</i> SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation |
| title_full | <i>ATP2A2</i> SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation |
| title_fullStr | <i>ATP2A2</i> SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation |
| title_full_unstemmed | <i>ATP2A2</i> SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation |
| title_short | <i>ATP2A2</i> SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation |
| title_sort | i atp2a2 i sine insertion in an irish terrier with darier disease and associated infundibular cyst formation |
| topic | <i>Canis lupus familiaris</i> dog dermatology skin desmosome acantholysis |
| url | https://www.mdpi.com/2073-4425/11/5/481 |
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