{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T20:34:51Z","timestamp":1767904491879,"version":"3.49.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,26]],"date-time":"2021-06-26T00:00:00Z","timestamp":1624665600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,26]],"date-time":"2021-06-26T00:00:00Z","timestamp":1624665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Genomics"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Glaucoma is a leading cause of visual disability and blindness. Release of iris pigment within the eye, pigment dispersion syndrome (PDS), can lead to one type of glaucoma known as pigmentary glaucoma. PDS has a genetic component, however, the genes involved with this condition are largely unknown. We sought to discover genes that cause PDS by testing cohorts of patients and controls for mutations using a tiered analysis of exome data.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Our primary analysis evaluated melanosome-related genes that cause dispersion of iris pigment in mice (<jats:italic>TYRP1<\/jats:italic>, <jats:italic>GPNMB<\/jats:italic>, <jats:italic>LYST<\/jats:italic>, <jats:italic>DCT<\/jats:italic>, and <jats:italic>MITF<\/jats:italic>). We identified rare mutations, but they were not statistically enriched in PDS patients. Our secondary analyses examined <jats:italic>PMEL<\/jats:italic> (previously linked with PDS), <jats:italic>MRAP<\/jats:italic>, and 19 other genes. Four <jats:italic>MRAP<\/jats:italic> mutations were identified in PDS cases but not in controls (<jats:italic>p<\/jats:italic>\u2009=\u20090.016). Immunohistochemical analysis of human donor eyes revealed abundant MRAP protein in the iris, the source of pigment in PDS. However, analysis of <jats:italic>MRAP<\/jats:italic> in additional cohorts (415 cases and 1645 controls) did not support an association with PDS. We also did not confirm a link between <jats:italic>PMEL<\/jats:italic> and PDS in our cohorts due to lack of reported mutations and similar frequency of the variants in PDS patients as in control subjects.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We did not detect a statistical enrichment of mutations in melanosome-related genes in human PDS patients and we found conflicting data about the likely pathogenicity of <jats:italic>MRAP<\/jats:italic> mutations. PDS may have a complex genetic basis that is not easily unraveled with exome analyses.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12864-021-07782-0","type":"journal-article","created":{"date-parts":[[2021,6,26]],"date-time":"2021-06-26T07:02:30Z","timestamp":1624690950000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Exome-based investigation of the genetic basis of human pigmentary glaucoma"],"prefix":"10.1186","volume":"22","author":[{"given":"Carly","family":"van der Heide","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wes","family":"Goar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kacie J.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wallace L. 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