{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T10:14:31Z","timestamp":1766139271434,"version":"3.44.0"},"reference-count":18,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Culler\u2013Jones syndrome (CJS) is an autosomal dominant disorder characterized by hypopituitarism, postaxial polydactyly, and craniofacial anomalies, associated with pathogenic <jats:italic>GLI2<\/jats:italic> variants. Genotype\u2013phenotype correlations suggest missense variants may present with isolated pituitary phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated an 8\u2010year\u2010old boy referred for short stature, failure to thrive, and neurodevelopmental concerns. Clinical assessment, endocrine evaluation, imaging studies, and trio exome sequencing were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patient exhibited growth hormone deficiency, dolichocephaly, midline diastema, lip and tongue ties, hypotonia, and ADHD. No polydactyly was noted. Trio exome sequencing revealed a de novo heterozygous likely pathogenic <jats:italic>GLI2<\/jats:italic> variant (c.1496G&gt;T; p.Arg499Leu) located within the DNA\u2010binding zinc finger domain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This case expands the phenotypic spectrum of <jats:italic>GLI2<\/jats:italic>\u2010related disorders and reinforces that non\u2010truncating <jats:italic>GLI2<\/jats:italic> variants are often associated with isolated hypopituitarism and subtle craniofacial or neurodevelopmental features. Genomic testing should be considered in similar clinical presentations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70136","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T04:25:01Z","timestamp":1757046301000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["De Novo <i>GLI2<\/i> Missense Variant in a Child With Isolated Hypopituitarism and Craniofacial Anomalies: Expanding the Phenotypic Spectrum"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6448-6618","authenticated-orcid":false,"given":"Himanshu","family":"Goel","sequence":"first","affiliation":[{"name":"Genomic Health  West Leederville Western Australia Australia"},{"name":"Hunter Genetics  Waratah New South Wales Australia"},{"name":"University of Newcastle  Callaghan New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrina","family":"Harrison","sequence":"additional","affiliation":[{"name":"Genomic Health  West Leederville Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-15-0009"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.13914"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-102249"},{"issue":"4","key":"e_1_2_12_5_1","first-page":"706","article-title":"GLI2 Mutations as a Cause of Hypopituitarism","volume":"9","author":"Cohen L. 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W.","year":"2023","journal-title":"Zhonghua Nei Ke Za Zhi"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1133492"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70136","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T06:47:43Z","timestamp":1758782863000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":18,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/mgg3.70136"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70136","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"2025-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70136"}}