{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:08:01Z","timestamp":1784092081700,"version":"3.55.0"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Ophthalmol."],"abstract":"<jats:p>\n                    Primary congenital glaucoma (PCG) is a rare developmental disorder caused by dysgenesis of the trabecular meshwork and anterior chamber angle. We report a five-year longitudinal case of severe bilateral PCG in a male presenting at two months of age with photophobia, tearing, corneal edema, and markedly elevated intraocular pressure (IOP). The patient required four surgical interventions, including deep sclerectomy with mitomycin C and trabeculotomy ab externo, to achieve long-term IOP control. Serial axial length measurements documented rapid buphthalmos, and ultrasound biomicroscopy revealed progressive posterior staphyloma, peripheral anterior synechiae, and iris thinning consistent with anterior segment dysgenesis (ASD). Whole exome sequencing identified compound heterozygosity:\n                    <jats:italic>CYP1B1<\/jats:italic>\n                    c.182G&amp;gt;A (p.G61E), the well-characterized Saudi founder mutation for PCG, and\n                    <jats:italic>CPAMD8<\/jats:italic>\n                    c.3061G&amp;gt;A (p.V102M), a novel ultra-rare variant predicted to be damaging. The coexistence of these two heterozygous variants in genes affecting complementary anterior segment developmental pathways supports a digenic inheritance model. To our knowledge, this is the first reported case of combined\n                    <jats:italic>CYP1B1<\/jats:italic>\n                    and\n                    <jats:italic>CPAMD8<\/jats:italic>\n                    variants in congenital glaucoma, underscoring the value of comprehensive genetic analysis in severe or atypical pediatric glaucoma presentations.\n                  <\/jats:p>","DOI":"10.3389\/fopht.2026.1829921","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:44:42Z","timestamp":1784090682000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["PCG with biallelic CYP1B1 and CPAMD8 variants: a longitudinal case report"],"prefix":"10.3389","volume":"6","author":[{"given":"Khaled","family":"Abu-Amero","sequence":"first","affiliation":[{"name":"Research Department, King Khaled Eye Specialist Hospital & Research Center","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gorka","family":"Sesma","sequence":"additional","affiliation":[{"name":"Pediatric Ophthalmology & Strabismus Division, King Khaled Eye Specialist Hospital & Research Center","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/archophthalmol.2010.41","article-title":"Incidence and clinical characteristics of childhood glaucoma: a population-based study","volume":"128","author":"Aponte","year":"2010","journal-title":"Arch Ophthalmol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.3.367","article-title":"Multiple CYP1B1 mutations and incomplete penetrance in an inbred population segregating primary congenital glaucoma suggest frequent de novo events and a dominant modifier locus","volume":"9","author":"Bejjani","year":"2000","journal-title":"Hum Mol Genet"},{"key":"B3","article-title":"Screening of CYP1B1 and LTBP2 genes in Saudi families with primary congenital glaucoma: genotype-phenotype correlation","volume":"17","author":"Abu-Amero","year":"2011","journal-title":"Mol Vis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4103\/2008-322x.156116","article-title":"Cytochrome P450 1B1 and primary congenital glaucoma","volume":"10","author":"Zhao","year":"2015","journal-title":"J Ophthalmic Vis Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2019.12.024","article-title":"Biallelic CPAMD8 variants are a frequent cause of childhood and juvenile open-angle glaucoma","volume":"127","author":"Siggs","year":"2020","journal-title":"Ophthalmology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-020-02164-0","article-title":"CPAMD8 loss-of-function underlies non-dominant congenital glaucoma with variable anterior segment dysgenesis and abnormal extracellular matrix","volume":"139","author":"Bonet-Fern\u00e1ndez","year":"2020","journal-title":"Hum Genet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1086\/338709","article-title":"Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene","volume":"70","author":"Vincent","year":"2002","journal-title":"Am J Hum Genet"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.7453\/gahmj.2013.008","article-title":"The CARE guidelines: consensus-based clinical case reporting guideline development","volume":"53","author":"Gagnier","year":"2013","journal-title":"Headache"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the ACMG and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13051222","article-title":"Genetic analysis of CYP1B1 and other anterior segment dysgenesis-associated genes in Latvian cohort of primary congenital glaucoma","volume":"13","author":"Elksne","year":"2025","journal-title":"Biomedicines"}],"container-title":["Frontiers in Ophthalmology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fopht.2026.1829921\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:44:50Z","timestamp":1784090690000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fopht.2026.1829921\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":10,"alternative-id":["10.3389\/fopht.2026.1829921"],"URL":"https:\/\/doi.org\/10.3389\/fopht.2026.1829921","relation":{},"ISSN":["2674-0826"],"issn-type":[{"value":"2674-0826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]},"article-number":"1829921"}}