{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T08:01:38Z","timestamp":1789718498827,"version":"4.0.1"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":260,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004681","name":"Higher Education Commission, Pakistan","doi-asserted-by":"publisher","award":["20-17501\/NRPU\/R&D\/HEC\/2021"],"award-info":[{"award-number":["20-17501\/NRPU\/R&D\/HEC\/2021"]}],"id":[{"id":"10.13039\/501100004681","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Primary congenital glaucoma (PCG) is an early\u2010onset eye disorder, particularly prevalent in populations with high consanguinity rates. In Pakistan, approximately 63% of marriages are reported to be consanguineous, contributing to an increased burden of autosomal\u2010recessive disorders. The genetic basis of PCG in the highly consanguineous Pakistani population is largely unexplored. This study was conducted to broaden the genetic landscape of PCG in families of Pakistani origin. PCG families identified through clinical characterization were recruited in the study. All probands were initially investigated for\n                    <jats:italic>CYP1B1<\/jats:italic>\n                    mutations by targeted Sanger sequencing, followed by segregation analysis of the identified variants. Moreover, one family (PCG02) not linked to\n                    <jats:italic>CYP1B1<\/jats:italic>\n                    was further subjected to a 250K SNP microarray and whole\u2010exome sequencing (WES). The study participants comprised nine large, unrelated consanguineous and three PCG trio families collected from Pakistan. Nine identified variants were recurrent, whereas one previously unreported variant,\n                    <jats:italic>CYP1B1<\/jats:italic>\n                    (NM_000104.4: c.1390T&gt;C; p.Ser464Pro), was not found in any of the online databases such as gnomAD, ClinVar, and dbSNP, and was predicted to be deleterious by all the pathogenicity predicting tools. Furthermore, a plausible 2\u2010Mb novel locus was identified on Chromosome 7q34 (139,681,371\u2010141,507,822) (GRCh38\/hg38) in family PCG02. The current study expands the mutation spectrum of\n                    <jats:italic>CYP1B1<\/jats:italic>\n                    in the Pakistani population and highlights the genetic heterogeneity of the disease in this population.\n                  <\/jats:p>","DOI":"10.1155\/humu\/1806353","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:02:01Z","timestamp":1789714921000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Uncovering the Novel Genetic Determinants of Primary Congenital Glaucoma in Pakistani Families"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4985-4763","authenticated-orcid":false,"given":"Hamza","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadia","family":"Bukhari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nauman","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israr Ahmed","family":"Bhutto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1239-9333","authenticated-orcid":false,"given":"Yousaf Jamal","family":"Mahsood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohsin Iqbal","family":"Haroon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8199-5959","authenticated-orcid":false,"given":"Muhammad Moeez","family":"Uddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal Shabir","family":"Memon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5591-1835","authenticated-orcid":false,"given":"Atta Ur","family":"Rehman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shah","family":"Zainab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5461-3599","authenticated-orcid":false,"given":"Asad","family":"Munir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8285-3482","authenticated-orcid":false,"given":"Syeda Hafiza Benish","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5207-2469","authenticated-orcid":false,"given":"Muhammad","family":"Ajmal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raheel","family":"Qamar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jibril","family":"Hirbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0170-3325","authenticated-orcid":false,"given":"Maleeha","family":"Azam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4320-7242","authenticated-orcid":false,"given":"Humaira","family":"Ayub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2019.05.003"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.3192"},{"key":"e_1_2_12_3_2","article-title":"The Third Genetic Locus (GLC3C) for Primary Congenital Glaucoma (PCG) Maps to Chromosome 14q24. 3","volume":"43","author":"Stoilov I. 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