{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T23:12:13Z","timestamp":1776726733814,"version":"3.51.2"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010473","name":"Bundesamt f\u00fcr Landwirtschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010473","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Animal Genetics"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Congenital malformations in cattle pose a diagnostic challenge with limited treatment options and are often associated with a guarded prognosis. The aim of this study was to characterize the clinicopathological phenotype of a viable calf with complex congenital heart defects and carpus valgus, and to identify a possible genetic cause using a whole genome sequencing trio approach. A 3\u2010month\u2010old female Holstein calf was referred for respiratory distress and congenital carpal deviation. Clinicopathologic findings included ventricular septal defect, ventricular dilatation, atrioventricular valve dysplasia, an overriding aorta, and unilateral carpus valgus. Genetic analysis revealed a private heterozygous missense variant in <jats:italic>BRI3BP<\/jats:italic> affecting an evolutionarily conserved residue (c.478G&gt;A; p.Val160Ile). The variant was predicted to be deleterious and was present only in the affected calf and was absent in more than 5100 sequenced bovine genomes, including both parents, indicating a de novo origin. This study implicates an important role for the uncharacterized BRI3 binding protein in cardiac and possibly also bone development. By presenting the first <jats:italic>BRI3BP<\/jats:italic>\u2010related disease model, this study demonstrates the potential to gain new insights into the function of individual genes by using phenotypically well\u2010studied spontaneous mutants in large animals, and it provides a novel candidate gene for similar conditions in humans.<\/jats:p>","DOI":"10.1111\/age.13494","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T05:15:09Z","timestamp":1732684509000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of a de novo missense variant in the <scp><i>BRI3BP<\/i><\/scp> gene in a Holstein calf with congenital cardiac malformation and carpus valgus"],"prefix":"10.1111","volume":"56","author":[{"given":"Chang","family":"He","sequence":"first","affiliation":[{"name":"Institute of Animal Pathology, Vetsuisse Faculty University of Bern  Bern Switzerland"},{"name":"Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty University of Bern  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9406-8844","authenticated-orcid":false,"given":"Lloren\u00e7","family":"Grau\u2010Roma","sequence":"additional","affiliation":[{"name":"Institute of Animal Pathology, Vetsuisse Faculty University of Bern  Bern Switzerland"},{"name":"Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty University of Bern  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6678-4661","authenticated-orcid":false,"given":"Robin","family":"Schmid","sequence":"additional","affiliation":[{"name":"Clinic for Ruminants, Department of Clinical Veterinary Medicine, Vetsuisse Faculty University of Bern  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5648-963X","authenticated-orcid":false,"given":"Irene M.","family":"H\u00e4fliger","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty University of Bern  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0191-5686","authenticated-orcid":false,"given":"Mireille","family":"Meylan","sequence":"additional","affiliation":[{"name":"Clinic for Ruminants, Department of Clinical Veterinary Medicine, Vetsuisse Faculty University of Bern  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9773-522X","authenticated-orcid":false,"given":"Cord","family":"Dr\u00f6gem\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty University of Bern  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6438-7975","authenticated-orcid":false,"given":"Joana G. 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