{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T23:58:28Z","timestamp":1760745508132,"version":"3.40.5"},"reference-count":21,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Polydactyly is a hallmark of <jats:italic>GLI3<\/jats:italic> pathogenic variants, with Greig cephalopolysyndactyly syndrome and Pallister\u2010Hall syndrome being the two main associated clinical presentations. Homozygous <jats:italic>GLI3<\/jats:italic> variants are rare instances in the literature, and mendelian dominance is the accepted framework for <jats:italic>GLI3<\/jats:italic>\u2010related diseases. Herein, we report three unrelated probands, presenting with polydactyly, and homozygous variants in the <jats:italic>GLI3<\/jats:italic> gene. First, a 10\u2010year\u2010old girl, whose parents were first\u2010degree cousins, presented with bilateral postaxial polydactyly of the hands, developmental delay and multiple malformations. Second, a male newborn, whose parents were first\u2010degree cousins, presented with isolated bilateral postaxial polysyndactyly of the hands and the feet. Third, an adult male, whose parents were first\u2010degree cousins, had bilateral mesoaxial polydactyly of the hands, with severe intellectual disability and multiple malformations. All three probands carried homozygous <jats:italic>GLI3<\/jats:italic> variants. Strikingly, the parents also carried the child's variant, in the heterozygous state, without any clinical sign of <jats:italic>GLI3<\/jats:italic> disease. Given the clinical presentation of our patients, the rarity and predicted high pathogenicity of the variants observed, and the absence of other pathogenic variants, we suggest that these <jats:italic>GLI3<\/jats:italic> homozygous variants are causal. Moreover, the parents were heterozygous for the observed variants, but were clinically unremarkable, suggesting that these variants are hypomorphic alleles.<\/jats:p>","DOI":"10.1002\/ajmg.a.62426","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T07:42:54Z","timestamp":1627026174000},"page":"3831-3837","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Homozygous <scp><i>GLI3<\/i><\/scp> variants observed in three unrelated patients presenting with syndromic polydactyly"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0776-4380","authenticated-orcid":false,"given":"Ahmed","family":"El Mouatani","sequence":"first","affiliation":[{"name":"Service Histologie\u2010Embryologie\u2010Cytog\u00e9n\u00e9tique H\u00f4pital Necker\u2010Enfants Malades, Assistance Publique \u2013 H\u00f4pitaux de Paris  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1808-4276","authenticated-orcid":false,"given":"G\u00e9raldine","family":"Van Winckel","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine G\u00e9n\u00e9tique Centre Hospitalier Universitaire Vaudois (CHUV)  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1272-4327","authenticated-orcid":false,"given":"Khaoula","family":"Zaafrane\u2010Khachnaoui","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale CHU de Nice, H\u00f4pital de l'Archet II  Nice France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9156-5047","authenticated-orcid":false,"given":"Sandra","family":"Whalen","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Fonctionnelle de G\u00e9n\u00e9tique Clinique Centre de R\u00e9f\u00e9rence Maladies Rares Anomalies du d\u00e9veloppement et syndromes malformatifs, H\u00f4pital Armand Trousseau, Assistance Publique \u2013 H\u00f4pitaux de Paris  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amale","family":"Achaiaa","sequence":"additional","affiliation":[{"name":"Service Histologie\u2010Embryologie\u2010Cytog\u00e9n\u00e9tique H\u00f4pital Necker\u2010Enfants Malades, Assistance Publique \u2013 H\u00f4pitaux de Paris  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6544-357X","authenticated-orcid":false,"given":"Sophie","family":"Kaltenbach","sequence":"additional","affiliation":[{"name":"Service Histologie\u2010Embryologie\u2010Cytog\u00e9n\u00e9tique H\u00f4pital Necker\u2010Enfants Malades, Assistance Publique \u2013 H\u00f4pitaux de Paris  Paris France"},{"name":"INSERM UMR 1163 Universit\u00e9 de Paris, Imagine Institute  Paris 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