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 (2023). Independent COL17A1 Variants in Cats with Junctional Epidermolysis Bullosa. Genes, 14(10) MDPI 10.3390/genes14101835

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Kiener, Sarah, Soto Martin, Sara, Letko, Anna, Jagannathan, Vidya, Leeb, Tosso

Subjects:

600 Technology > 630 Agriculture
500 Science > 590 Animals (Zoology)

ISSN:

2073-4425

Publisher:

MDPI

Language:

English

Submitter:

Pubmed Import

Date Deposited:

30 Oct 2023 13:57

Last Modified:

07 Aug 2024 15:44

Publisher DOI:

10.3390/genes14101835

PubMed ID:

37895184

Uncontrolled Keywords:

Felis catus JEB WGS animal model dermatology precision medicine skin splicing

BORIS DOI:

10.48350/188265

URI:

https://boris.unibe.ch/id/eprint/188265

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