{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:13:10Z","timestamp":1777518790989,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,5,13]],"date-time":"2020-05-13T00:00:00Z","timestamp":1589328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"European Union Horizon 2020 research and innovation program under the Marie Sk\u0142odowska-Curie","award":["675033"],"award-info":[{"award-number":["675033"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Axenfeld\u2010Rieger syndrome (ARS) is a rare autosomal dominant disorder that affects the anterior segment of the eye. The aim of this study was to examine the <jats:italic>PITX2<\/jats:italic> gene to identify possible novel mutations in Pakistani and Mexican families affected by the ARS phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three unrelated probands with a diagnosis of ARS were recruited for this study. Genomic DNA was isolated from the peripheral blood of the probands and their family members. Polymerase chain reaction and Sanger sequencing were used for the analysis of coding exons and the flanking intronic regions of the <jats:italic>PITX2<\/jats:italic> gene. Bioinformatics tools and database (VarSome, Provean, and MutationTaster, SIFT, PolyPhen\u20102, and HOPE) were evaluated to explore missense variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified novel heterozygous variations in the <jats:italic>PITX2<\/jats:italic> gene that segregated with the ARS phenotype within the families. The variant NM_153426.2(<jats:italic>PITX2<\/jats:italic>):c.226G\u00a0&gt;\u00a0T or p.(Ala76Ser) and the mutation NM_153426.2(<jats:italic>PITX2<\/jats:italic>):c.455G\u00a0&gt;\u00a0A or p.(Cys152Tyr) were identified in two Pakistani pedigrees, and the mutation NM_153426.2(<jats:italic>PITX2<\/jats:italic>):c.242_265del or p.(Lys81_Gln88del), segregated in a Mexican family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study extends the spectrum of <jats:italic>PITX2<\/jats:italic> mutations in individuals with ARS, enabling an improved diagnosis of this rare but serious syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1215","type":"journal-article","created":{"date-parts":[[2020,5,13]],"date-time":"2020-05-13T07:53:50Z","timestamp":1589356430000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel mutations in the <i>PITX2<\/i> gene in Pakistani and Mexican families with Axenfeld\u2010Rieger syndrome"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4931-7327","authenticated-orcid":false,"given":"Valeria","family":"Lo Faro","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics University Medical Center (UMC) University of Amsterdam (UvA) Amsterdam The Netherlands"},{"name":"Department of Ophthalmology University Medical Center Groningen (UMCG) University of Groningen (RUG) Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sorath N.","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology and Strabismus Al\u2010Shifa Eye Trust Hospital Rawalpindi Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad I.","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Donders Institute for Brain Cognition and Behaviour Radboud UMC Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Villanueva\u2010Mendoza","sequence":"additional","affiliation":[{"name":"Department of Genetics Asociaci\u00f3n Para Evitar la Ceguera en M\u00e9xico M\u00e9xico M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vianney","family":"Cort\u00e9s\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Genetics Asociaci\u00f3n Para Evitar la Ceguera en M\u00e9xico M\u00e9xico M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nomdo","family":"Jansonius","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University Medical Center Groningen (UMCG) University of Groningen (RUG) Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur A. B.","family":"Bergen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics University Medical Center (UMC) University of Amsterdam (UvA) Amsterdam The Netherlands"},{"name":"Department of Ophthalmology Universitair Medische Centre (UMC) University of Amsterdam (UvA) Amsterdam The Netherlands"},{"name":"The Netherlands Institute for Neurosciences (NIN\u2010KNAW) Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shazia","family":"Micheal","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics University Medical Center (UMC) University of Amsterdam (UvA) Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,13]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(00)00525-0"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1076\/opge.25.1.57.29002"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-0979"},{"issue":"6","key":"e_1_2_6_5_1","first-page":"1297","article-title":"Closing in on the Rieger syndrome gene on 4q25: Mapping translocation breakpoints within a 50\u2010kb region","volume":"59","author":"Datson N. A.","year":"1996","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5309"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.7.743"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi365"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2010.0036"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-3251"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/13816810.2018.1547911"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399405010082"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2006.02.006"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12804"},{"issue":"7","key":"e_1_2_6_15_1","first-page":"321","article-title":"Variability of clinical manifestations in the family with Axenfeld\u2010Rieger syndrome]","volume":"109","author":"Kami\u0144ska A.","year":"2007","journal-title":"Klinika Oczna"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty897"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.14.2131"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-7-59"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-015-0462-0"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000065602"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.16.1631"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx251"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.80"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.6.1968-1982.2003"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008592200"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20226"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/aos.13030"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13148"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0195971"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1296-392"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-0472"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/212656"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36540"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.93"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-548"},{"issue":"12","key":"e_1_2_6_36_1","first-page":"1448","article-title":"Identification of four new PITX2 gene mutations in patients with Axenfeld\u2010Rieger syndrome","volume":"1","author":"Vieira V.","year":"2006","journal-title":"Molecular Vision"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.163"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-019-0840-9"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmgg3.1215","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1215","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.1215","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1215","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T13:33:28Z","timestamp":1694007208000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.1215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,13]]},"references-count":37,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1002\/mgg3.1215"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.1215","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,13]]},"assertion":[{"value":"2020-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1215"}}