{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:42:03Z","timestamp":1790066523570,"version":"4.0.1"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T00:00:00Z","timestamp":1680652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011842","name":"Finnish National Agency for Education","doi-asserted-by":"publisher","award":["OPH-363-2022"],"award-info":[{"award-number":["OPH-363-2022"]}],"id":[{"id":"10.13039\/501100011842","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Helsinki","award":["OPH-363-2022"],"award-info":[{"award-number":["OPH-363-2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Polydactyly is a rare autosomal dominant or recessive appendicular patterning defect of the hands and feet, phenotypically characterized by the duplication of digits. Postaxial polydactyly (PAP) is the most common form and includes two main types: PAP type A (PAPA) and PAP type B (PAPB). Type A involves a well-established extra digit articulated with the fifth or sixth metacarpal, while type B presents a rudimentary or poorly developed superfluous digit. Pathogenic variants in several genes have been identified in isolated and syndromic forms of polydactyly. The current study presents two Pakistani families with autosomal recessive PAPA with intra- and inter-familial phenotype variability. Whole-exome sequencing and Sanger analysis revealed a novel missense variant in KIAA0825 (c.3572C&gt;T: p.Pro1191Leu) in family A and a known nonsense variant in GLI1 (c.337C&gt;T: p.Arg113*) in family B. In silico studies of mutant KIAA0825 and GLI1 proteins revealed considerable structural and interactional modifications that suggest an abnormal function of the proteins leading to the disease phenotype. The present study broadens the mutational spectrum of KIAA0825 and demonstrates the second case of a previously identified GLI1 variant with variable phenotypes. These findings facilitate genetic counseling in Pakistani families with a polydactyly-related phenotype.<\/jats:p>","DOI":"10.3390\/genes14040869","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T02:59:43Z","timestamp":1680663583000},"page":"869","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of GLI1 and KIAA0825 Variants in Two Families with Postaxial Polydactyly"],"prefix":"10.3390","volume":"14","author":[{"given":"Safeer","family":"Ahmad","sequence":"first","affiliation":[{"name":"Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, Pakistan"},{"name":"Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki 00290, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Zeeshan","family":"Ali","sequence":"additional","affiliation":[{"name":"Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Muzammal","sequence":"additional","affiliation":[{"name":"Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amjad Ullah","family":"Khan","sequence":"additional","affiliation":[{"name":"Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Ikram","sequence":"additional","affiliation":[{"name":"Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Muurinen","sequence":"additional","affiliation":[{"name":"Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki 00290, Finland"},{"name":"Children\u2019s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki 00290, Finland"},{"name":"Folkh\u00e4lsan Research Center, Folkh\u00e4lsan Institute of Genetics, Helsinki 00290, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabir","family":"Hussain","sequence":"additional","affiliation":[{"name":"Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki 00290, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Loid","sequence":"additional","affiliation":[{"name":"Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki 00290, Finland"},{"name":"Children\u2019s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki 00290, Finland"},{"name":"Folkh\u00e4lsan Research Center, Folkh\u00e4lsan Institute of Genetics, Helsinki 00290, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8591-0377","authenticated-orcid":false,"given":"Muzammil Ahmad","family":"Khan","sequence":"additional","affiliation":[{"name":"Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4547-001X","authenticated-orcid":false,"given":"Outi","family":"M\u00e4kitie","sequence":"additional","affiliation":[{"name":"Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki 00290, Finland"},{"name":"Children\u2019s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki 00290, Finland"},{"name":"Folkh\u00e4lsan Research Center, Folkh\u00e4lsan Institute of Genetics, Helsinki 00290, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/cga.12163","article-title":"Clinical study of 459 polydactyly cases in China, 2010 to 2014","volume":"56","author":"Xiang","year":"2016","journal-title":"Congenit. 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