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Ectopia lentis in humans and other species is reported to be caused by trauma, genetic variants, and systemic diseases. The most commonly reported genetic causes are dominant alleles in\n                    <jats:italic>FBN1<\/jats:italic>\n                    . Here we examined a 3-day old Oldenburg x Thoroughbred colt due to concerns over bilateral ocular anomalies and hypothesized that either a recessively inherited allele or a dominant\n                    <jats:italic>de novo<\/jats:italic>\n                    allele was the genetic cause. Examination revealed bilateral microphakia and spherophakia with medioventral lens subluxation. Histopathology of the globes was consistent with ectopia lentis. Whole genome sequencing of the affected foal was conducted, and forty-six candidate genes were evaluated for SNVs and small INDELS. Testing both hypotheses, 82 variants were identified, of which 69 were present in publicly available data from 504 horses and not investigated further. Of the 13 remaining variants, two variants were found in 3\u2019 UTRs (\n                    <jats:italic>ADAMTS17<\/jats:italic>\n                    and\n                    <jats:italic>OAF<\/jats:italic>\n                    ), ten were intronic, and one was a coding variant located in the\n                    <jats:italic>FBN1<\/jats:italic>\n                    gene encoding fibrillin-1 (FBN1:p.(Ala882Val)). This variant was also computationally predicted to be deleterious to protein function, including in silico modelling of FBN1 which suggests that 882Val impacts disulfide bond formation by Van der Waals clashing in a hybrid domain of the protein. The affected foal was confirmed by Sanger sequencing to be heterozygous for this variant and his clinically unaffected dam, reportedly unaffected sire, and five paternal half-siblings were homozygous for the reference allele. Additionally, the homologous human substitution is reported to be pathogenic, causing Marfan syndrome with a dominant mode of inheritance, of which ectopia lentis is a common feature. These findings support the\n                    <jats:italic>de novo<\/jats:italic>\n                    hypothesis with\n                    <jats:italic>FBN1<\/jats:italic>\n                    :p.(Ala882Val) as the likely cause of ectopia lentis in this foal, the first genetic explanation for this condition in the horse. Given the role of\n                    <jats:italic>FBN1<\/jats:italic>\n                    in ectopia lentis in humans and other species,\n                    <jats:italic>FBN1<\/jats:italic>\n                    should be evaluated as a potential candidate when other horses with this condition are identified.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-21139-7","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T08:46:40Z","timestamp":1761295600000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A de novo FBN1 variant likely causes congenital bilateral ectopia lentis in a crossbred horse"],"prefix":"10.1038","volume":"15","author":[{"given":"Elizabeth","family":"Esdaile","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristopher","family":"Houston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley J.","family":"Till","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger. 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No other authors have a conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Hair and blood samples from the affected foal, dam, and his paternal half-siblings were collected under the ethical review provided by the UC Davis Institutional Animal Care and Use Committee as part of Protocol #22786 and experiments were performed according to what was reviewed. A hair sample from the sire was provided by Weatherbys Scientific on behalf of the Coloured Horse and Pony Society (UK) (CHAPS UK) as part of a previously banked sample for registration. The ocular exam and euthanasia were performed at the request of the owner following standard of care and Royal College of Veterinary Surgeons (RCVS) code of practice. 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