{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T18:03:27Z","timestamp":1783101807117,"version":"3.54.6"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2010,6,25]],"date-time":"2010-06-25T00:00:00Z","timestamp":1277424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We report on the novel association of trigonocephaly and polysyndactyly in two unrelated patients due to mutations within the last third (exon 14) and first third (exon 6) of the<jats:italic>GLI3<\/jats:italic>gene, respectively.<jats:italic>GLI3<\/jats:italic>acts as a downstream mediator of the Sonic hedgehog signal\u2010transduction pathway which is essential for early development; and plays a role in cell growth, specialization, and patterning of structures such as the brain and limbs.<jats:italic>GLI3<\/jats:italic>mutations have been identified in patients with Pallister\u2013Hall, Grieg cephalopolysyndactyly syndrome (GCPS), postaxial polydactyly type A1, preaxial polydactyly type IV, and in one patient with acrocallosal syndrome (ACLS). Furthermore, deletions including the<jats:italic>GLI3<\/jats:italic>gene have been reported in patients with features of GCPS and ACLS. To date, trigonocephaly has not been associated with abnormalities of<jats:italic>GLI3<\/jats:italic>and craniosynostosis is not a feature of GCPS. However, Hootnick and Holmes reported on a father with polysyndactyly and son with trigonocephaly, polysyndactyly, and agenesis of the corpus callosum, considered GCPS thereafter. Guzzetta et al. subsequently described a patient with trigonocephaly, polysyndactyly, and agenesis of the corpus callosum postulating a diagnosis of GCPS, later considered ACLS. In retrospect, these two patients, evaluated prior to mutational analysis, and our patients, with confirmed mutations, likely fall within the<jats:italic>GLI3<\/jats:italic>morphopathy spectrum and may provide a bridge to better understanding those patients with overlapping features of GCPS and ACLS. Based on this observation, we suggest<jats:italic>GLI3<\/jats:italic>studies in patients presenting with this constellation of findings, specifically metopic craniosynostosis with polysyndactyly, in order to provide appropriate medical management and genetic counseling. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33495","type":"journal-article","created":{"date-parts":[[2010,6,26]],"date-time":"2010-06-26T06:53:40Z","timestamp":1277535220000},"page":"1654-1660","source":"Crossref","is-referenced-by-count":36,"title":["Metopic craniosynostosis due to mutations in<i>GLI3<\/i>: A novel association"],"prefix":"10.1002","volume":"152A","author":[{"given":"Donna 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