{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:26:18Z","timestamp":1790198778176,"version":"4.1.0"},"reference-count":97,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research","doi-asserted-by":"publisher","award":["BSC-0123"],"award-info":[{"award-number":["BSC-0123"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research","doi-asserted-by":"publisher","award":["ELGV1707"],"award-info":[{"award-number":["ELGV1707"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010055","name":"University of Salford","doi-asserted-by":"publisher","award":["BSC-0123"],"award-info":[{"award-number":["BSC-0123"]}],"id":[{"id":"10.13039\/100010055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010055","name":"University of Salford","doi-asserted-by":"publisher","award":["ELGV1707"],"award-info":[{"award-number":["ELGV1707"]}],"id":[{"id":"10.13039\/100010055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Glaucoma is the largest cause of irreversible blindness with a multifactorial genetic etiology. This study explores novel genes and gene networks in familial forms of primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) to identify rare mutations with high penetrance. Thirty-one samples from nine MYOC-negative families (five POAG and four PACG) underwent whole-exome sequencing and analysis. A set of prioritized genes and variations were screened in an independent validation cohort of 1536 samples and the whole-exome data from 20 sporadic patients. The expression profiles of the candidate genes were analyzed in 17 publicly available expression datasets from ocular tissues and single cells. Rare, deleterious SNVs in AQP5, SRFBP1, CDH6 and FOXM1 from POAG families and in ACACB, RGL3 and LAMA2 from PACG families were found exclusively in glaucoma cases. AQP5, SRFBP1 and CDH6 also revealed significant altered expression in glaucoma in expression datasets. Single-cell expression analysis revealed enrichment of identified candidate genes in retinal ganglion cells and corneal epithelial cells in POAG; whereas for PACG families, retinal ganglion cells and Schwalbe\u2019s Line showed enriched expression. Through an unbiased exome-wide search followed by validation, we identified novel candidate genes for familial cases of POAG and PACG. The SRFBP1 gene found in a POAG family is located within the GLC1M locus on Chr5q. Pathway analysis of candidate genes revealed enrichment of extracellular matrix organization in both POAG and PACG.<\/jats:p>","DOI":"10.3390\/genes14020495","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T02:28:27Z","timestamp":1676514507000},"page":"495","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Whole Exome Sequencing Reveals Novel Candidate Genes in Familial Forms of Glaucomatous Neurodegeneration"],"prefix":"10.3390","volume":"14","author":[{"given":"Kiran","family":"Narta","sequence":"first","affiliation":[{"name":"Genomics & Molecular Medicine, CSIR-Institute of Genomics & Integrative Biology, Mathura Road (Near Sukhdev Vihar), New Delhi 110025, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8637-6919","authenticated-orcid":false,"given":"Manoj Ramesh","family":"Teltumbade","sequence":"additional","affiliation":[{"name":"Genomics & Molecular Medicine, CSIR-Institute of Genomics & Integrative Biology, Mathura Road (Near Sukhdev Vihar), New Delhi 110025, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansi","family":"Vishal","sequence":"additional","affiliation":[{"name":"Genomics & Molecular Medicine, CSIR-Institute of Genomics & Integrative Biology, Mathura Road (Near Sukhdev Vihar), New Delhi 110025, India"},{"name":"CSIR-Indian Institute of Chemical Biology, Raja S. 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Mullick Road, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samreen","family":"Sadaf","sequence":"additional","affiliation":[{"name":"Genomics & Molecular Medicine, CSIR-Institute of Genomics & Integrative Biology, Mathura Road (Near Sukhdev Vihar), New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8278-8396","authenticated-orcid":false,"given":"Mohd.","family":"Faruq","sequence":"additional","affiliation":[{"name":"Genomics & Molecular Medicine, CSIR-Institute of Genomics & Integrative Biology, Mathura Road (Near Sukhdev Vihar), New Delhi 110025, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hodan","family":"Jama","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naushin","family":"Waseem","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Rao","sequence":"additional","affiliation":[{"name":"L. V. Prasad Eye Institute, Bhubaneswar 751024, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijit","family":"Sen","sequence":"additional","affiliation":[{"name":"Drishti Pradip, Kolkata 700068, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunal","family":"Ray","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India"},{"name":"CSIR-Indian Institute of Chemical Biology, Raja S. C. Mullick Road, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1089-7179","authenticated-orcid":false,"given":"Arijit","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Genomics & Molecular Medicine, CSIR-Institute of Genomics & Integrative Biology, Mathura Road (Near Sukhdev Vihar), New Delhi 110025, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India"},{"name":"Translational Medicine Unit, Biomedical Research & Innovation Centre, University of Salford, Salford M5 4WT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global Prevalence of Glaucoma and Projections of Glaucoma Burden through 2040: A systematic review and meta-analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1076\/soph.17.2.69.14722","article-title":"Angle closure: Classification, concepts, and the role of ultrasound biomicroscopy in diagnosis and treatment","volume":"17","author":"Tello","year":"2002","journal-title":"Semin. 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