{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T02:21:11Z","timestamp":1768875671755,"version":"3.49.0"},"reference-count":12,"publisher":"Georg Thieme Verlag KG","issue":"02","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Klin Padiatr"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Background GLI3 is a transcriptional regulator of several genes involved in mammalian skeletal development. Mutations in the pleiotropic gene GLI3 may result in different inherited disorders including Greig cephalopolysyndactyly syndrome (GCPS). GCPS is characterized by mild to severe craniofacial and limb malformations.<\/jats:p><jats:p>Methods and Results Here, we report clinical and molecular study of 3 families with GCPS originated in different regions of Pakistan. Sanger sequencing revealed two novel variants including a frameshift [c. 3790_3791InsC, p.(Gly1236Argfs*11)] and a missense [c.1692A&gt;G, p.(His536Arg)], and one previously reported variant [c.1965_1966delAT, p.(His627Glufs*48)] located in 2 different domains of the GLI3.<\/jats:p><jats:p>Conclusion This study not only expanded spectrum of the mutations in the GLI3 but also highlighted phenotypic variability in the GCPS patients. This will facilitate diagnosis and genetic counseling of families with same and related disorders in the Pakistani population.<\/jats:p>","DOI":"10.1055\/a-1223-2489","type":"journal-article","created":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T00:16:38Z","timestamp":1608336998000},"page":"53-58","source":"Crossref","is-referenced-by-count":7,"title":["Greig Cephalopolysyndactyly Syndrome: Phenotypic Variability Associated with Variants in Two Different Domains of GLI3"],"prefix":"10.1055","volume":"233","author":[{"given":"Hammal","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biosciences, COMSATS University, Islamabad, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sohail","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, University of Balochistan, Quetta, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadia","family":"Nawaz","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wasim","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Arshad","family":"Rafiq","sequence":"additional","affiliation":[{"name":"Department of Biosciences, COMSATS University, Islamabad, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Abdullah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2020,12,18]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1089\/gtmb.2019.0071","article-title":"Variants in GLI3 Cause Greig Cephalopolysyndactyly Syndrome","volume":"23","author":"Abdullah","year":"2019","journal-title":"Genet Test Mol Bioma"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1750-1172-3-10","article-title":"The Greig cephalopolysyndactyly syndrome","volume":"3","author":"LG Biesecker","year":"2008","journal-title":"Orphanet J Rare Dis"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1136\/jmg.2004.029181","article-title":"What you can learn from one gene: GLI3","volume":"43","author":"LG Biesecker","year":"2006","journal-title":"J Med Genet"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"8143","DOI":"10.1074\/jbc.274.12.8143","article-title":"Sonic Hedgehog-induced Activation of the Gli1 Promoter Is Mediated by GLI3","volume":"274","author":"P Dai","year":"1999","journal-title":"J Biol Chem"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"3205","DOI":"10.1242\/dev.126.14.3205","article-title":"Gli proteins encode context-dependent positive and negative functions: implications for development and disease","volume":"126","author":"AR Altaba","year":"1999","journal-title":"Development"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13000-017-0682-8","article-title":"Novel GLI3 variant causing overlapped Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS) phenotype with agenesis of gallbladder and pancreas","volume":"13","author":"S Ito","year":"2018","journal-title":"Diagn Pathol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1086\/429346","article-title":"Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: robust phenotype prediction from the type and position of GLI3 mutations","volume":"76","author":"J J Johnston","year":"2005","journal-title":"Am J Hum Genet"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera \u2013 a visualization system for exploratory research and analysis","volume":"25","author":"E F Pettersen","year":"2004","journal-title":"J Comput Chem"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1086\/302557","article-title":"The phenotypic spectrum of GLI3 morphopathies includes autosomal dominant preaxial polydactyly type-IV and postaxial polydactyly type-A\/B; No phenotype prediction from the position of GLI3 mutations","volume":"65","author":"U Radhakrishna","year":"1999","journal-title":"Am J Hum Genet"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"S Richards","year":"2015","journal-title":"Genet Med"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.ydbio.2007.07.023","article-title":"Hoxd and Gli3 interactions modulate digit number in the amniote limb","volume":"310","author":"R Sheth","year":"2007","journal-title":"Dev Biol"},{"key":"ref12","first-page":"14","article-title":"The genetics of hand malformations","author":"S A Temtamy","year":"1978","journal-title":"Birth Defects"}],"container-title":["Klinische P\u00e4diatrie"],"original-title":[],"language":"de","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1223-2489.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T23:36:37Z","timestamp":1670369797000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1223-2489"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,18]]},"references-count":12,"journal-issue":{"issue":"02","published-online":{"date-parts":[[2021,3,8]]},"published-print":{"date-parts":[[2021,3]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1223-2489","relation":{},"ISSN":["0300-8630","1439-3824"],"issn-type":[{"value":"0300-8630","type":"print"},{"value":"1439-3824","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,18]]}}}