{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T10:02:13Z","timestamp":1779789733034,"version":"3.53.1"},"reference-count":10,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T00:00:00Z","timestamp":1749945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T00:00:00Z","timestamp":1749945600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ras\u2010responsive element binding protein 1 (RREB1) is a zinc finger transcription factor that is crucial in regulating cell growth, gene expression, and DNA repair. It functions as both a repressor and an activator, with its activity controlled by the MAPK signaling pathway. RREB1 has been implicated in various conditions such as type 2 diabetes (T2D), obesity, and cancer, suggesting its potential as both a biomarker and a therapeutic target for these diseases. While several cases of 6p terminal deletions in the\n                    <jats:italic>RREB1<\/jats:italic>\n                    gene and one case of Noonan\u2010like RASopathy due to a loss\u2010of\u2010function variant have been reported, this study presents the first case of a pathogenic loss\u2010of\u2010function variant in RREB1 associated with morbid obesity and metabolic disturbances. Our patient, a 16\u2010year\u2010old male, exhibited morbid obesity, metabolic disorders, moderate intellectual disability, and atypical autism symptoms. He was referred to our clinic by the pediatric endocrinology department for genetic evaluation. Initial genetic testing included karyotype analysis and SNP array testing with 700\u2009000 probes. Whole exome sequencing (WES) was then performed on the patient and his family, revealing a de novo novel variant, c.3178_3179del, p.(Glu1060Argfs*37) in the\n                    <jats:italic>RREB1<\/jats:italic>\n                    gene, which was confirmed by Sanger sequencing. This novel variant underscores the critical role of RREB1 in regulating metabolic processes, particularly obesity. Additionally, the patient's neurodevelopmental delay aligns with previously reported findings of RREB1 loss\u2010of\u2010function variants. These results highlight the need for further research to fully understand the metabolic implications of\n                    <jats:italic>RREB1<\/jats:italic>\n                    gene loss, with this study providing valuable insights for future investigations.\n                  <\/jats:p>","DOI":"10.1111\/cge.70001","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T02:41:14Z","timestamp":1750041674000},"page":"130-135","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["First Report of a Novel Pathogenic Variant in the\n                    <i>RREB1<\/i>\n                    Gene Associated With Obesity and Metabolic Syndrome"],"prefix":"10.1111","volume":"109","author":[{"given":"Nurana","family":"Mammadova","sequence":"first","affiliation":[{"name":"Department of Medical Genetics School of Medicine, Erciyes University  Kayseri T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Baki","family":"Yildirim","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics School of Medicine, Erciyes University  Kayseri T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nihal","family":"Hatipoglu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics School of Medicine, Erciyes University  Kayseri T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munis","family":"Dundar","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics School of Medicine, Erciyes University  Kayseri T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.10.5335"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20090342"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.8.1009"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003681"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902053"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14496"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-022-05856-6"},{"key":"e_1_2_11_9_1","unstructured":"G. Z.Yu N. A. J.Krentz L.Bentley et\u00a0al. \u201cLoss of RREB1 Reduces Adipogenesis and Improves Insulin Sensitivity in Mouse and Human Adipocytes \u201d(2024) bioRxiv: The Preprint Server for Biology."},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-020-01276-7"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.40834"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70001","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70001","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T09:03:18Z","timestamp":1779786198000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,15]]},"references-count":10,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/cge.70001"],"URL":"https:\/\/doi.org\/10.1111\/cge.70001","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.70001\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.70001\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.70001\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.70001\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.70001\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,15]]},"assertion":[{"value":"2025-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}