ATP2A2 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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ftmdpi:oai:mdpi.com:/2073-4425/11/5/481/ 2023-08-20T04:05:49+02:00 ATP2A2 SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation Monika Linek Maren Doelle Tosso Leeb Anina Bauer Fabienne Leuthard Jan Henkel Danika Bannasch Vidhya Jagannathan Monika M. Welle agris 2020-04-28 application/pdf https://doi.org/10.3390/genes11050481 EN eng Multidisciplinary Digital Publishing Institute Animal Genetics and Genomics https://dx.doi.org/10.3390/genes11050481 https://creativecommons.org/licenses/by/4.0/ Genes; Volume 11; Issue 5; Pages: 481 Canis lupus familiaris dog dermatology skin desmosome acantholysis calcium animal model veterinary medicine precision medicine Text 2020 ftmdpi https://doi.org/10.3390/genes11050481 2023-07-31T23:26:02Z 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. Text Canis lupus MDPI Open Access Publishing Genes 11 5 481 |
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Open Polar |
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MDPI Open Access Publishing |
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ftmdpi |
language |
English |
topic |
Canis lupus familiaris dog dermatology skin desmosome acantholysis calcium animal model veterinary medicine precision medicine |
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Canis lupus familiaris dog dermatology skin desmosome acantholysis calcium animal model veterinary medicine precision medicine Monika Linek Maren Doelle Tosso Leeb Anina Bauer Fabienne Leuthard Jan Henkel Danika Bannasch Vidhya Jagannathan Monika M. Welle ATP2A2 SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation |
topic_facet |
Canis lupus familiaris dog dermatology skin desmosome acantholysis calcium animal model veterinary medicine precision medicine |
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 (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. |
format |
Text |
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 |
title |
ATP2A2 SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation |
title_short |
ATP2A2 SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation |
title_full |
ATP2A2 SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation |
title_fullStr |
ATP2A2 SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation |
title_full_unstemmed |
ATP2A2 SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation |
title_sort |
atp2a2 sine insertion in an irish terrier with darier disease and associated infundibular cyst formation |
publisher |
Multidisciplinary Digital Publishing Institute |
publishDate |
2020 |
url |
https://doi.org/10.3390/genes11050481 |
op_coverage |
agris |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_source |
Genes; Volume 11; Issue 5; Pages: 481 |
op_relation |
Animal Genetics and Genomics https://dx.doi.org/10.3390/genes11050481 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3390/genes11050481 |
container_title |
Genes |
container_volume |
11 |
container_issue |
5 |
container_start_page |
481 |
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1774716555344478208 |