{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T08:01:56Z","timestamp":1780992116253,"version":"3.54.1"},"reference-count":64,"publisher":"American Society for Clinical Investigation","issue":"17","license":[{"start":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:00:00Z","timestamp":1694131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002996","name":"Dutch Heart Foundation","doi-asserted-by":"crossref","award":["03-003-2020-T062"],"award-info":[{"award-number":["03-003-2020-T062"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The CRC-1213","award":["Project B01"],"award-info":[{"award-number":["Project B01"]}]},{"name":"The Sonderforschungsbereich\/Transregio 23","award":["Project C08"],"award-info":[{"award-number":["Project C08"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,8]]},"abstract":"<jats:p>\n                    Pediatric cardiomyopathy (CM) represents a group of rare, severe disorders that affect the myocardium. To date, the etiology and mechanisms underlying pediatric CM are incompletely understood, hampering accurate diagnosis and individualized therapy development. Here, we identified biallelic variants in the highly conserved flightless-I (\n                    <jats:italic>FLII<\/jats:italic>\n                    ) gene in 3 families with idiopathic, early-onset dilated CM. We demonstrated that patient-specific\n                    <jats:italic>FLII<\/jats:italic>\n                    variants, when brought into the zebrafish genome using CRISPR\/Cas9 genome editing, resulted in the manifestation of key aspects of morphological and functional abnormalities of the heart, as observed in our patients. Importantly, using these genetic animal models, complemented with in-depth loss-of-function studies, we provided insights into the function of Flii during ventricular chamber morphogenesis in vivo, including myofibril organization and cardiomyocyte cell adhesion, as well as trabeculation. In addition, we identified Flii function to be important for the regulation of Notch and Hippo signaling, crucial pathways associated with cardiac morphogenesis and function. Taken together, our data provide experimental evidence for a role for FLII in the pathogenesis of pediatric CM and report biallelic variants as a genetic cause of pediatric CM.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.168247","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T12:01:08Z","timestamp":1691668868000},"source":"Crossref","is-referenced-by-count":9,"title":["Biallelic variants in FLII cause pediatric cardiomyopathy by disrupting cardiomyocyte cell adhesion and myofibril organization"],"prefix":"10.1172","volume":"8","author":[{"given":"Claudine W.B.","family":"Ruijmbeek","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filomena","family":"Housley","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics, Max Planck Institute for 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