{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T20:27:14Z","timestamp":1761164834633,"version":"build-2065373602"},"reference-count":66,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Hypertrophic cardiomyopathy (HCM) is a naturally occurring cardiac disorder afflicting humans, cats, rhesus macaques, pigs, and rarely dogs. The disease is characterized by maladaptive left ventricular wall thickening. Over 1500 sarcomere-coding mutations explain HCM in humans, whereas only 3 have been reported in cat breeds. To date, no mutations have been described in dogs. HCM in a nuclear family of Golden Retrievers was identified following the sudden cardiac death of 3 related puppies &lt;2 years of age from 2 dam-offspring repeat matings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Whole-genome sequencing on the 3 affected puppies, along with nuclear family members (ie, sire, dam, 4 unaffected littermates, 4 unaffected half-siblings), and 1 distantly related, geriatric, cardiovascularly normal Golden Retriever was performed (n=14). Candidate variant genotyping was performed in an unphenotyped cohort of dogs (n=2771) and an expanded population of phenotyped, unrelated Golden Retrievers (n=45). Left ventricular tissue immunofluorescence staining was subsequently performed to investigate incorporation and expression of mutant protein within the cardiac sarcomere of HCM-affected cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Gross and histopathologic evaluations of the HCM-affected puppies revealed hallmark features of the disease, including cardiomyocyte hypertrophy, interstitial fibrosis, and left-sided congestive heart failure. Segregation analysis of called variants, performed under assumptions of an autosomal-recessive mode of inheritance, identified a single segregating c.593C&gt;T missense variant in\n                      <jats:italic toggle=\"yes\">TNNI3<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">Cardiac Troponin-I<\/jats:italic>\n                      ). This variant was not observed in the unphenotyped (n=2771) nor in the phenotyped, unrelated cohort of dogs (n=45). Immunofluorescence staining of left ventricular tissues did not reveal obvious aberrant protein localization and expression at the sarcomeric level, suggesting the molecular pathogenesis of the\n                      <jats:italic toggle=\"yes\">TNNI3<\/jats:italic>\n                      variant is not related to abnormal protein incorporation within the sarcomere.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>This variant represents the first-ever reported HCM-associated variant in any canine species, and its identification holds promise for establishing translational models, genetic screening, and early disease prevention within the breed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circgen.125.005096","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T09:00:15Z","timestamp":1755853215000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Novel\n                    <i>Cardiac Troponin-I<\/i>\n                    Missense Variant (c.593C&gt;T) Is Associated With Familial Hypertrophic Cardiomyopathy in Golden Retrievers"],"prefix":"10.1161","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5016-3743","authenticated-orcid":true,"given":"Victor N.","family":"Rivas","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences (V.N.R., M.W.V., R.H.L.L., S.M.L., M.L., J.A.S.), North Carolina State University, College of Veterinary Medicine, Raleigh."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dayna A.","family":"Goldsmith","sequence":"additional","affiliation":[{"name":"Faculty of 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