{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:50:10Z","timestamp":1791366610126,"version":"4.3.1"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Exper Ophthalmology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Retinitis pigmentosa GTPase regulator (\n                      <jats:italic>RPGR<\/jats:italic>\n                      )\u2010associated retinal dystrophies are among the most severe inherited retinal diseases (IRDs), yet population\u2010level data from Southern Europe remain scarce.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This nationwide, multicentre study characterises the clinical and genetic spectrum of\n                      <jats:italic>RPGR<\/jats:italic>\n                      \u2010associated disease in Portugal, integrating multimodal imaging, standardised phenotyping and curated molecular analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 103 individuals from 40 families (58 males; 45 heterozygous females) were identified using the IRD\u2010PT registry. Males predominantly manifested X\u2010linked retinitis pigmentosa (82.8%) with childhood\/adolescence onset (mean 13.1\u2009\u00b1\u20098.8\u2009years), whereas cone\/cone\u2010rod dystrophy (17.2%) presented later in life. Visual acuity in males (mean 0.65\u2009\u00b1\u20090.54 logMAR) matched international cohorts, showing an age\u2010dependent decline. Female heterozygotes demonstrated striking variability: although central vision was generally preserved (mean 0.39\u2009\u00b1\u20090.55 logMAR), fundus autofluorescence (FAF) revealed a wide spectrum from normal to male\u2010pattern disease. FAF severity correlated strongly with visual acuity, with male\u2010pattern heterozygotes showing significantly reduced visual acuity. Interocular asymmetry was present in 20.5% of females. Twenty\u2010nine distinct\n                      <jats:italic>RPGR<\/jats:italic>\n                      variants were identified, including 11 novel; truncating variants predominated, particularly within ORF15, accounting for 63% of genetically confirmed cases. Genotype\u2013phenotype relationships aligned with established patterns, with distal\n                      <jats:italic>RPGR<\/jats:italic>\n                      variants associated with cone\u2010dominant disease and proximal variants with rod\u2010cone dystrophy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study provides the first nationwide overview of\n                      <jats:italic>RPGR<\/jats:italic>\n                      \u2010associated disease in Portugal, expanding the mutational landscape and reinforcing the clinical utility of FAF phenotyping in female heterozygotes. These findings support harmonised phenotyping and full\u2010length\n                      <jats:italic>RPGR<\/jats:italic>\n                      sequencing to improve diagnosis, counselling, and readiness for emerging gene\u2010based therapies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ceo.70149","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T01:16:44Z","timestamp":1785287804000},"page":"943-954","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and Genetic Landscape of\n                    <scp>\n                      <i>RPGR<\/i>\n                    <\/scp>\n                    \u2010Associated Retinal Dystrophies in Portugal: Insights From the Nationwide\n                    <scp>IRD<\/scp>\n                    \u2010\n                    <scp>PT<\/scp>\n                    Registry"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8230-1805","authenticated-orcid":false,"given":"Nuno","family":"Cruz","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Hospitais da Universidade de Coimbra (HUC), Unidade Local de Sa\u00fade de Coimbra (ULSC)  Coimbra Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC)  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2907-0091","authenticated-orcid":false,"given":"C\u00e9lia Azevedo","family":"Soares","sequence":"additional","affiliation":[{"name":"Medical Science Department University of Aveiro  Aveiro Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Porto 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