{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:41:33Z","timestamp":1789756893927,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,9,23]],"date-time":"2014-09-23T00:00:00Z","timestamp":1411430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001641","name":"Glaucoma Research Foundation","doi-asserted-by":"publisher","award":["no grant number"],"award-info":[{"award-number":["no grant number"]}],"id":[{"id":"10.13039\/100001641","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010327","name":"Glaucoomfonds","doi-asserted-by":"crossref","award":["Uitzicht 2013-5"],"award-info":[{"award-number":["Uitzicht 2013-5"]}],"id":[{"id":"10.13039\/501100010327","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010321","name":"Oogfonds","doi-asserted-by":"crossref","award":["Uitzicht 2013-5"],"award-info":[{"award-number":["Uitzicht 2013-5"]}],"id":[{"id":"10.13039\/501100010321","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010374","name":"Stichting Blindenhulp","doi-asserted-by":"crossref","award":["no grant number"],"award-info":[{"award-number":["no grant number"]}],"id":[{"id":"10.13039\/501100010374","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Exper Ophthalmology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>CYP1B<\/jats:italic><\/jats:styled-content>1<\/jats:italic> is the most commonly mutated gene in primary congenital glaucoma (PCG<\/jats:styled-content>), and mutations have also been identified in primary open\u2010angle glaucoma (POAG<\/jats:styled-content>). This study was undertaken to describe mutations in CYP1B<\/jats:italic><\/jats:styled-content>1<\/jats:italic> in patients and families with PCG<\/jats:styled-content> and POAG<\/jats:styled-content> from P<\/jats:styled-content>akistan.<\/jats:p><\/jats:sec>Design<\/jats:title>Case\u2010control series.<\/jats:p><\/jats:sec>Participants<\/jats:title>Forty families, 190 sporadic POAG<\/jats:styled-content> cases and 140 controls from P<\/jats:styled-content>akistan.<\/jats:p><\/jats:sec>Methods<\/jats:title>Patients and healthy individuals of one consanguineous P<\/jats:styled-content>akistani family were genotyped with high\u2010resolution single nucleotide polymorphism microarrays. Homozygosity mapping was performed using H<\/jats:styled-content>omozygosityM<\/jats:styled-content>apper. Direct sequencing of CYP1B<\/jats:italic><\/jats:styled-content>1<\/jats:italic> gene was performed in probands of the families, sporadic POAG<\/jats:styled-content> cases and control individuals.<\/jats:p><\/jats:sec>Main Outcome Measures<\/jats:title>Mutations in the CYP1B<\/jats:italic><\/jats:styled-content>1<\/jats:italic> gene in PCG<\/jats:styled-content> and POAG<\/jats:styled-content> patients.<\/jats:p><\/jats:sec>Results<\/jats:title>Homozygosity mapping in a consanguineous P<\/jats:styled-content>akistani family revealed one 11\u2010Mb homozygous region encompassing the CYP1B<\/jats:italic><\/jats:styled-content>1<\/jats:italic> gene. A homozygous CYP1B<\/jats:italic><\/jats:styled-content>1<\/jats:italic> missense mutation (p.Arg390H<\/jats:styled-content>is) was identified in this family. Sequence analysis of CYP1B<\/jats:italic><\/jats:styled-content>1<\/jats:italic> in 39 additional families revealed one known and three novel homozygous mutations in PCG<\/jats:styled-content> (p.Ala288P<\/jats:styled-content>ro, p.Asp242A<\/jats:styled-content>la, p.A<\/jats:styled-content>rg355* and p.Arg290P<\/jats:styled-content>rofs*37). In POAG<\/jats:styled-content>, one novel heterozygous missense mutation (p.Asp316V<\/jats:styled-content>al) was identified in one family and a previously reported mutation (p.Glu229L<\/jats:styled-content>ys) was identified in three families. Analysis of CYP1B<\/jats:italic><\/jats:styled-content>1<\/jats:italic> in a panel of 190 sporadic POAG<\/jats:styled-content> patients revealed three novel heterozygous variants (p.Thr234L<\/jats:styled-content>ys, p.Ala287P<\/jats:styled-content>ro and p.G<\/jats:styled-content>ln362*) and three previously reported heterozygous variants (p.Gly61G<\/jats:styled-content>lu, p.Glu229L<\/jats:styled-content>ys and p.Arg368H<\/jats:styled-content>is). The p.Glu229L<\/jats:styled-content>ys variant was significantly associated with POAG (P<\/jats:italic>\u2009=\u20090.03; odds ratio 2.49).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>This study confirms that CYP1B<\/jats:italic><\/jats:styled-content>1<\/jats:italic> mutations are associated with POAG<\/jats:styled-content> and PCG<\/jats:styled-content> in the P<\/jats:styled-content>akistani population.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ceo.12369","type":"journal-article","created":{"date-parts":[[2014,8,5]],"date-time":"2014-08-05T10:41:07Z","timestamp":1407235267000},"page":"31-39","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Identification of novel CYP1B<\/i><\/scp>1<\/i> gene mutations in patients with primary congenital and primary open\u2010angle glaucoma"],"prefix":"10.1111","volume":"43","author":[{"given":"Shazia","family":"Micheal","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humaira","family":"Ayub","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Radboud University Medical Centre Nijmegen The Netherlands"},{"name":"Department of Biosciences COMSATS Institute of Information Technology Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saemah N","family":"Zafar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology Al\u2010Shifa Eye Trust Hospital Rawalpindi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjorn","family":"Bakker","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmood","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology Al\u2010Shifa Eye Trust Hospital Rawalpindi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Akhtar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology Al\u2010Shifa Eye Trust Hospital Rawalpindi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farrah","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology Al\u2010Shifa Eye Trust Hospital Rawalpindi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad I","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Centre Nijmegen The Netherlands"},{"name":"Department of Biosciences COMSATS Institute of Information 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