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Independent COL17A1 Variants in Cats with Junctional Epidermolysis Bullosa

Epidermolysis bullosa (EB), characterized by defective adhesion of the epidermis to the dermis, is a heterogeneous disease with many subtypes in human patients and domestic animals. We investigated two unrelated cats with recurring erosions and ulcers on ear pinnae, oral mucosa, and paw pads that we...

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Autores principales: Kiener, Sarah, Troyer, Heather, Ruvolo, Daniel, Grest, Paula, Soto, Sara, Letko, Anna, Jagannathan, Vidhya, Leeb, Tosso, Mauldin, Elizabeth A., Yang, Ching, Rostaher, Ana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606533/
https://www.ncbi.nlm.nih.gov/pubmed/37895184
http://dx.doi.org/10.3390/genes14101835
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author Kiener, Sarah
Troyer, Heather
Ruvolo, Daniel
Grest, Paula
Soto, Sara
Letko, Anna
Jagannathan, Vidhya
Leeb, Tosso
Mauldin, Elizabeth A.
Yang, Ching
Rostaher, Ana
author_facet Kiener, Sarah
Troyer, Heather
Ruvolo, Daniel
Grest, Paula
Soto, Sara
Letko, Anna
Jagannathan, Vidhya
Leeb, Tosso
Mauldin, Elizabeth A.
Yang, Ching
Rostaher, Ana
author_sort Kiener, Sarah
collection PubMed
description Epidermolysis bullosa (EB), characterized by defective adhesion of the epidermis to the dermis, is a heterogeneous disease with many subtypes in human patients and domestic animals. We investigated two unrelated cats with recurring erosions and ulcers on ear pinnae, oral mucosa, and paw pads that were suggestive of EB. Histopathology confirmed the diagnosis of EB in both cats. Case 1 was severe and had to be euthanized at 5 months of age. Case 2 had a milder course and was alive at 11 years of age at the time of writing. Whole genome sequencing of both affected cats revealed independent homozygous variants in COL17A1 encoding the collagen type XVII alpha 1 chain. Loss of function variants in COL17A1 lead to junctional epidermolysis bullosa (JEB) in human patients. The identified splice site variant in case 1, c.3019+1del, was predicted to lead to a complete deficiency in collagen type XVII. Case 2 had a splice region variant, c.769+5G>A. Assessment of the functional impact of this variant on the transcript level demonstrated partial aberrant splicing with residual expression of wildtype transcript. Thus, the molecular analyses provided a plausible explanation of the difference in clinical severity between the two cases and allowed the refinement of the diagnosis in the affected cats to JEB. This study highlights the complexity of EB in animals and contributes to a better understanding of the genotype-phenotype correlation in COL17A1-related JEB.
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spelling pubmed-106065332023-10-28 Independent COL17A1 Variants in Cats with Junctional Epidermolysis Bullosa Kiener, Sarah Troyer, Heather Ruvolo, Daniel Grest, Paula Soto, Sara Letko, Anna Jagannathan, Vidhya Leeb, Tosso Mauldin, Elizabeth A. Yang, Ching Rostaher, Ana Genes (Basel) Article Epidermolysis bullosa (EB), characterized by defective adhesion of the epidermis to the dermis, is a heterogeneous disease with many subtypes in human patients and domestic animals. We investigated two unrelated cats with recurring erosions and ulcers on ear pinnae, oral mucosa, and paw pads that were suggestive of EB. Histopathology confirmed the diagnosis of EB in both cats. Case 1 was severe and had to be euthanized at 5 months of age. Case 2 had a milder course and was alive at 11 years of age at the time of writing. Whole genome sequencing of both affected cats revealed independent homozygous variants in COL17A1 encoding the collagen type XVII alpha 1 chain. Loss of function variants in COL17A1 lead to junctional epidermolysis bullosa (JEB) in human patients. The identified splice site variant in case 1, c.3019+1del, was predicted to lead to a complete deficiency in collagen type XVII. Case 2 had a splice region variant, c.769+5G>A. Assessment of the functional impact of this variant on the transcript level demonstrated partial aberrant splicing with residual expression of wildtype transcript. Thus, the molecular analyses provided a plausible explanation of the difference in clinical severity between the two cases and allowed the refinement of the diagnosis in the affected cats to JEB. This study highlights the complexity of EB in animals and contributes to a better understanding of the genotype-phenotype correlation in COL17A1-related JEB. MDPI 2023-09-22 /pmc/articles/PMC10606533/ /pubmed/37895184 http://dx.doi.org/10.3390/genes14101835 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kiener, Sarah
Troyer, Heather
Ruvolo, Daniel
Grest, Paula
Soto, Sara
Letko, Anna
Jagannathan, Vidhya
Leeb, Tosso
Mauldin, Elizabeth A.
Yang, Ching
Rostaher, Ana
Independent COL17A1 Variants in Cats with Junctional Epidermolysis Bullosa
title Independent COL17A1 Variants in Cats with Junctional Epidermolysis Bullosa
title_full Independent COL17A1 Variants in Cats with Junctional Epidermolysis Bullosa
title_fullStr Independent COL17A1 Variants in Cats with Junctional Epidermolysis Bullosa
title_full_unstemmed Independent COL17A1 Variants in Cats with Junctional Epidermolysis Bullosa
title_short Independent COL17A1 Variants in Cats with Junctional Epidermolysis Bullosa
title_sort independent col17a1 variants in cats with junctional epidermolysis bullosa
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606533/
https://www.ncbi.nlm.nih.gov/pubmed/37895184
http://dx.doi.org/10.3390/genes14101835
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