{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:33:28Z","timestamp":1787772808084,"version":"build-2784847793"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>To identify the pathogenic variants associated with primary open-angle glaucoma (POAG) using whole-exome sequencing (WES) data of a large South Indian family.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We recruited a large five-generation South Indian family (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 84) with a positive family history of POAG (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 19). All study participants had a comprehensive ocular evaluation. We performed WES for 16 samples (nine POAG and seven unaffected controls) since Sanger sequencing of the POAG candidate genes (\n                      <jats:italic toggle=\"yes\">MYOC<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">OPTN<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">TBK1<\/jats:italic>\n                      ) showed no genetic variation. We used an in-house pipeline for prioritizing the pathogenic variants based on their segregation among the POAG individual.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>We identified one novel and five low-frequency pathogenic variants with consistent co-segregation in all affected individuals. The variant c.G3719A in RPGR-interacting domain of RPGRIP1 that segregated heterozygously with the six POAG cases is distinct from variants causing photoreceptor dystrophies, reported affecting the RPGR protein complex signaling in primary cilia. The cilia in trabecular meshwork (TM) cells has been reported to mediate the intraocular pressure (IOP) sensation. Furthermore, we identified a novel c.A1295G variant in Rho guanine nucleotide exchange factors Gene 40 (ARHGEF40) and a likely pathogenic variant in the RPGR gene, suggesting that they may alter the RhoA activity essential for IOP regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our study supports that low-frequency pathogenic variants in multiple genes and pathways probably affect Primary Open Angle Glaucoma\u2019s pathogenesis in the large South Indian family. Furthermore, it requires larger case-controls to perform family-based association tests and to strengthen our analysis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/ijo.ijo_3301_20","type":"journal-article","created":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T23:07:16Z","timestamp":1630537636000},"page":"2461-2468","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["Whole-exome sequencing identifies multiple pathogenic variants in a large South Indian family with primary open-angle glaucoma"],"prefix":"10.4103","volume":"69","author":[{"given":"Mohd Hussain","family":"Shah","sequence":"first","affiliation":[{"name":"Genetics, Aravind Medical Research Foundation, Madurai, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manojkumar","family":"Kumaran","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Aravind Medical Research Foundation, Madurai, Tamil Nadu, India"},{"name":"Department of School of Chemical and Biotechnology, SASTRA (Deemed to be University), Thanjavur, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash","family":"Chermakani","sequence":"additional","affiliation":[{"name":"Genetics, Aravind Medical Research Foundation, Madurai, Tamil Nadu, India"},{"name":"Department of Molecular Biology, Alagappa University, Karaikudi, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohideen Abdul","family":"Kader","sequence":"additional","affiliation":[{"name":"Department of Glaucoma Clinic, Aravind Eye Hospital, Tirunelveli, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Ramakrishnan","sequence":"additional","affiliation":[{"name":"Department of Glaucoma Clinic, Aravind Eye Hospital, Tirunelveli, Tamil Nadu, 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