{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T10:45:46Z","timestamp":1777805146293,"version":"3.51.4"},"reference-count":15,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:00:00Z","timestamp":1773532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:00:00Z","timestamp":1773532800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100008968","name":"Istanbul Kalkinma Ajansi","doi-asserted-by":"publisher","award":["TR10\/22\/TNH\/0001"],"award-info":[{"award-number":["TR10\/22\/TNH\/0001"]}],"id":[{"id":"10.13039\/501100008968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Child Neurol"],"abstract":"<jats:p>\n                    Periodic reanalysis of genomic data plays a pivotal role in refining variant interpretation and resolving previously undiagnosed cases, particularly in the context of rare diseases. We report a female patient presenting with global developmental delay, drug-resistant epilepsy, optic atrophy, congenital heart defects, and craniofacial dysmorphism. An initially deprioritized heterozygous\n                    <jats:italic toggle=\"yes\">NOTCH1<\/jats:italic>\n                    variant (NM_017617.5: c.4787T&gt;C; p.Leu1596Pro), previously associated with isolated cardiac phenotypes, was later reclassified as likely pathogenic following annual reanalysis through our institutional pipeline. Trio-based whole exome sequencing confirmed the variant's de novo origin, and emerging literature published in 2024 expanded the phenotypic spectrum of\n                    <jats:italic toggle=\"yes\">NOTCH1<\/jats:italic>\n                    -related disorders to include neurologic, ocular, musculoskeletal, craniofacial, and integumentary features\u2014closely mirroring the patient's presentation. This diagnostic refinement enabled tailored clinical management and informed genetic counseling. This case underscores the clinical utility of systematic genomic reanalysis in rare disease diagnostics, where evolving knowledge enables reclassification of previously uncertain variants. Moreover, this case adds to the growing body of evidence, broadening the recognized clinical and molecular landscape of\n                    <jats:italic toggle=\"yes\">NOTCH1<\/jats:italic>\n                    -related disorders.\n                  <\/jats:p>","DOI":"10.1177\/08830738261422860","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T06:15:23Z","timestamp":1773641723000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Periodic Genetic Reanalysis Identifies a Novel De Novo\n                    <i>NOTCH1<\/i>\n                    Variant: A Case Report"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3982-5303","authenticated-orcid":false,"given":"Eylul","family":"Aydin","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, Graduate School of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8210-9002","authenticated-orcid":false,"given":"Aybike S.","family":"Bulut","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Graduate School of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1929-8394","authenticated-orcid":false,"given":"Berkay","family":"Yildiz","sequence":"additional","affiliation":[{"name":"School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0321-5936","authenticated-orcid":false,"given":"Ulas","family":"Ozonur","sequence":"additional","affiliation":[{"name":"School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2647-6416","authenticated-orcid":false,"given":"Ozkan","family":"Ozdemir","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Graduate School of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey"},{"name":"School of Medicine, Department of Basic Sciences, Department of Medical Biology, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey"},{"name":"Acibadem Mehmet Ali Aydinlar University Rare Diseases and Orphan Drugs Application and Research Center (ACURARE), Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaya","family":"Bilguvar","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Graduate School of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey"},{"name":"Acibadem Mehmet Ali Aydinlar University Rare Diseases and Orphan Drugs Application and Research Center (ACURARE), Istanbul, Turkey"},{"name":"School of Medicine, Department of Basic Sciences, Department of Medical Genetics, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey"},{"name":"Yale School of Medicine, Department of Neurosurgery, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7728-6527","authenticated-orcid":false,"given":"Ozden Hatirnaz","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Graduate School of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey"},{"name":"School of Medicine, Department of Basic Sciences, Department of Medical Biology, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey"},{"name":"Acibadem Mehmet Ali Aydinlar University Rare Diseases and Orphan Drugs Application and Research Center (ACURARE), Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Burak","family":"Tatli","sequence":"additional","affiliation":[{"name":"Istanbul Pediatric Neurology Clinic, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8310-4053","authenticated-orcid":false,"given":"Ozlem","family":"Akgun-Dogan","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Graduate School of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey"},{"name":"Acibadem Mehmet Ali Aydinlar University Rare Diseases and Orphan Drugs Application and Research Center (ACURARE), Istanbul, Turkey"},{"name":"School of Medicine, Department of Pediatrics, Division of Pediatric Genetics, Acibadem Mehmet Ali Aydinlar University, Istanbul, 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