{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T05:17:18Z","timestamp":1768886238174,"version":"3.49.0"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"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":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Polydactyly is a limb malformation and can occur as nonsyndromic polydactyly, syndromic polydactyly, or along with other limb defects. A few genes have been identified that cause various forms of syndromic and nonsyndromic polydactyly, of which <jats:italic>GLI3<\/jats:italic> has been extensively explored. In the present study, <jats:italic>GLI3<\/jats:italic> gene was screened by direct resequencing in 15 polydactyly cases with or without other anomalies. <jats:italic>GLI3<\/jats:italic> screening revealed two novel pathogenic variants, NM_000168.6:c.3414delC [p.(H1138Qfs*68)] and NM_000168.6:c.1862C&gt;T [p.(P621L)], found in two unrelated cases of familial complex pre\u2010 and postaxial polysyndactyly and sporadic Greig cephalopolysyndactyly syndrome (GCPS), respectively. The first pathogenic <jats:italic>GLI3<\/jats:italic> variant, NM_000168.6:c.3414delC, causes premature protein truncation at the C\u2010terminal domain of GLI3. Alternatively, the second pathogenic variant, NM_000168.6:c.1862C&gt;T, lies in the DNA binding domain of GLI3 protein and may affect its hydrophobic interaction with DNA. Both pathogenic <jats:italic>GLI3<\/jats:italic> variants had reduced transcriptional activity in HEK293 cells that likely had led to haploinsufficiency and, consequently, the clinical phenotypes. Overall, the present study reports a novel familial case of complex pre\u2010 and postaxial polysyndactyly and the underlying novel pathogenic <jats:italic>GLI3<\/jats:italic> variant expanding the clinical criteria for <jats:italic>GLI3<\/jats:italic> mutational spectrum to complex pre\u2010 and postaxial polysyndactyly. Furthermore, this study also reports a novel <jats:italic>GLI3<\/jats:italic> pathogenic variant linked to GCPS, highlighting the known genotype\u2013phenotype correlation.<\/jats:p>","DOI":"10.1002\/ajmg.a.61919","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T09:45:37Z","timestamp":1602755137000},"page":"97-104","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Novel <scp><i>GLI3<\/i> pathogenic<\/scp> variants in complex pre\u2010 and postaxial polysyndactyly and Greig cephalopolysyndactyly syndrome"],"prefix":"10.1002","volume":"185","author":[{"given":"Rashmi","family":"Patel","sequence":"first","affiliation":[{"name":"Centre for Genetic Disorders, Institute of Science Banaras Hindu University  Varanasi Uttar Pradesh India"},{"name":"National Cancer Institute National Institute of Health  Frederick MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subodh Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery G S Memorial Plastic Surgery Hospital &amp; Trauma Center  Varanasi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Visweswar","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences Banaras Hindu University  Varanasi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2444-8400","authenticated-orcid":false,"given":"Akhtar","family":"Ali","sequence":"additional","affiliation":[{"name":"Centre for Genetic Disorders, Institute of Science Banaras Hindu University  Varanasi Uttar Pradesh India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-3-10"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/429346"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21328"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007471"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080860"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0722.2012.00986.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33495"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cga.12139"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mgene.2014.11.002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8378770"},{"key":"e_1_2_9_12_1","unstructured":"Preacher K. 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