{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T22:27:31Z","timestamp":1781562451390,"version":"3.54.5"},"reference-count":42,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T00:00:00Z","timestamp":1651190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030_200354"],"award-info":[{"award-number":["310030_200354"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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 pro\u03b11 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&gt;T or p.(Lys1172*), and c.3066del or p.(Gly1023Valfs*50) for cases no. 1, 2&amp;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.<\/jats:p>","DOI":"10.3390\/genes13050797","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T16:49:57Z","timestamp":1651250997000},"page":"797","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Independent COL5A1 Variants in Cats with Ehlers-Danlos Syndrome"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2714-2370","authenticated-orcid":false,"given":"Sarah","family":"Kiener","sequence":"first","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"},{"name":"Dermfocus, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-0795","authenticated-orcid":false,"given":"Neoklis","family":"Apostolopoulos","sequence":"additional","affiliation":[{"name":"Anicura Kleintierspezialisten Augsburg, 86157 Augsburg, Germany"},{"name":"Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Schissler","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, James L. Voss Veterinary Teaching Hospital, Fort Collins, CO 80525, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8491-9174","authenticated-orcid":false,"given":"Pascal-Kolja","family":"Hass","sequence":"additional","affiliation":[{"name":"Division of Veterinary Anatomy, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Leuthard","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"},{"name":"Dermfocus, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8155-0041","authenticated-orcid":false,"given":"Vidhya","family":"Jagannathan","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Schuppisser","sequence":"additional","affiliation":[{"name":"VET Zentrum AG, 8422 Pfungen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3777-8724","authenticated-orcid":false,"given":"Sara","family":"Soto","sequence":"additional","affiliation":[{"name":"Dermfocus, University of Bern, 3001 Bern, Switzerland"},{"name":"Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Welle","sequence":"additional","affiliation":[{"name":"Dermfocus, University of Bern, 3001 Bern, Switzerland"},{"name":"Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9028-7604","authenticated-orcid":false,"given":"Ursula","family":"Mayer","sequence":"additional","affiliation":[{"name":"Anicura Kleintierspezialisten Augsburg, 86157 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-4880","authenticated-orcid":false,"given":"Tosso","family":"Leeb","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"},{"name":"Dermfocus, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0142-226X","authenticated-orcid":false,"given":"Nina M.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4500-8191","authenticated-orcid":false,"given":"Sabine","family":"Kaessmeyer","sequence":"additional","affiliation":[{"name":"Dermfocus, University of Bern, 3001 Bern, Switzerland"},{"name":"Division of Veterinary Anatomy, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41572-020-0194-9","article-title":"The Ehlers\u2013Danlos syndromes","volume":"6","author":"Malfait","year":"2020","journal-title":"Nat. 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