Independent COL5A1 Variant in Cats with Ehlers-Danlos Syndrome

Kiener, Sarah; Apostolopoulos, Neoklis; Schissler, Jennifer; Hass, Pascal-Kolja; Leuthard, Fabienne; Jagannathan, Vidhya; Schuppisser, Carole; Soto, Sara; Welle, Monika; Mayer, Ursula; Leeb, Tosso; Fischer, Nina M; Kaessmeyer, Sabine (2022). Independent COL5A1 Variant in Cats with Ehlers-Danlos Syndrome. Genes, 13(5), p. 797. MDPI, Molecular Diversity Preservation International 10.3390/genes13050797

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We investigated four cats with similar clinical skin-related signs strongly suggestive of Ehlers-Danlos syndrome (EDS). Cases no. 1 and 4 were unrelated and the remaining two cases, no. 2 and 3, were reportedly siblings. Histopathological changes were characterized by severely altered dermal collagen fibers. Transmission electron microscopy in one case demonstrated abnormalities in the collagen fibril organization and structure. The genomes of the two unrelated affected cats and one of the affected siblings were sequenced and individually compared to 54 feline control genomes. We searched for private protein changing variants in known human EDS candidate genes and identified three independent heterozygous COL5A1 variants. COL5A1 is a well-characterized candidate gene for classical EDS. It encodes the proα1 chain of type V collagen, which is needed for correct collagen fibril formation and the integrity of the skin. The identified variants in COL5A1 are c.112_118+15del or r.spl?, c.3514A>T or p.(Lys1172*), and c.3066del or p.(Gly1023Valfs*50) for cases no. 1, 2&3, and 4, respectively. They presumably all lead to nonsense-mediated mRNA decay, which results in haploinsufficiency of COL5A1 and causes the alterations of the connective tissue. The whole genome sequencing approach used in this study enables a refinement of the diagnosis for the affected cats as classical EDS. It further illustrates the potential of such experiments as a precision medicine approach in animals with inherited diseases.

Item Type:

Journal Article (Original Article)

Division/Institute:

09 Interdisciplinary Units > Next Generation Sequencing (NGS) Platform
05 Veterinary Medicine > Research Foci > DermFocus
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) > Veterinary Anatomy
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)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Kiener, Sarah; Hass, Pascal-Kolja; Leuthard, Fabienne Nadja; Jagannathan, Vidya; Soto Martin, Sara; Welle, Monika Maria; Leeb, Tosso and Kässmeyer, Sabine

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)
600 Technology > 610 Medicine & health

ISSN:

2073-4425

Publisher:

MDPI, Molecular Diversity Preservation International

Language:

English

Submitter:

Barbara Drews

Date Deposited:

04 May 2022 15:46

Last Modified:

28 Sep 2022 07:46

Publisher DOI:

10.3390/genes13050797

PubMed ID:

35627182

BORIS DOI:

10.48350/169632

URI:

https://boris.unibe.ch/id/eprint/169632

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