{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T08:49:02Z","timestamp":1790412542115,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T00:00:00Z","timestamp":1558396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Polydactyly is a common genetic limb deformity characterized by the presence of extra fingers or toes. This anomaly may occur in isolation (nonsyndromic) or as part of a syndrome. The disease is broadly divided into preaxial polydactyly (PPD; duplication of thumb), mesoaxial polydactyly (complex polydactyly), and postaxial polydactyly (PAP: duplication of the fifth finger). The extra digits may be present in one or both the limbs. Heterozygous variants in the <jats:italic>GLI3<\/jats:italic>, <jats:italic>ZRS<\/jats:italic>\/<jats:italic>SHH<\/jats:italic>, and <jats:italic>PITX1<\/jats:italic> have been associated with autosomal dominant polydactyly, while homozygous variants in the <jats:italic>ZNF141<\/jats:italic>, <jats:italic>IQCE<\/jats:italic>, <jats:italic>GLI1<\/jats:italic>, and <jats:italic>FAM92A<\/jats:italic> have been associated with autosomal recessive polydactyly. Pathogenic mutations in the <jats:italic>GLI3<\/jats:italic> gene (glioma\u2010associated oncogene family zinc finger 3) have been associated with both nonsyndromic and syndromic polydactyly.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we report an extended five generation kindred having 12 affected individuals exhibiting nonsyndromic postaxial polydactyly type A condition. Whole\u2010exome sequencing followed by variant prioritization, bioinformatic studies, Sanger validation, and segregation analysis was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using exome sequencing in the three affected individuals, we identified a novel heterozygous frameshift variant (c.3567_3568insG; p.Ala1190Glyfs*57) in the transcriptional activator (TA2) domain of the GLI3 encoding gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>To the best of our knowledge, the present study reports on the first familial case of nonsyndromic postaxial polydactyly due to the <jats:italic>GLI3<\/jats:italic> variant in Pakistani population. Our study also demonstrated the important role of GLI3 in causing nonsyndromic postaxial polydactyly.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.627","type":"journal-article","created":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T05:44:05Z","timestamp":1558503845000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Exome sequencing revealed a novel loss\u2010of\u2010function variant in the GLI3 transcriptional activator 2 domain underlies nonsyndromic postaxial polydactyly"],"prefix":"10.1002","volume":"7","author":[{"given":"Muhammad","family":"Umair","sequence":"first","affiliation":[{"name":"Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC) King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard\u2010Health Affairs (MNGHA) Riyadh Saudi 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Bin Abdulaziz University for Health Sciences, Ministry of National Guard\u2010Health Affairs (MNGHA) Riyadh Saudi Arabia"},{"name":"Division of Genetics, Department of Pediatrics King Abdullah Specialized Children\u2019s Hospital (KASCH) Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasim","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4294-6825","authenticated-orcid":false,"given":"Sulman","family":"Basit","sequence":"additional","affiliation":[{"name":"Center for Genetics and Inherited Diseases Taibah University Medina Saudi 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