{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:34:43Z","timestamp":1792276483190,"version":"4.4.0"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Exper Ophthalmology"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>With the promise of gene replacement therapy, eligible males and females with X\u2010linked inherited retinal dystrophy (XL\u2010IRD) should be identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Retrospective observational cohort study to establish the phenotypic and genotypic spectrum of XL\u2010IRD within New Zealand (NZ). Thirty\u2010two probands, including 9 females, with molecularly proven XL\u2010IRD due to <jats:italic>RP2<\/jats:italic> or <jats:italic>RPGR<\/jats:italic> mutations, and 72 family members, of which 43 were affected, were identified from the NZ IRD Database. Comprehensive ophthalmic phenotyping, familial cosegregation, genotyping, and bioinformatics were undertaken. Main outcome measures were: <jats:italic>RP2 and RPGR<\/jats:italic> pathogenic variant spectrum, phenotype in males and females (symptoms, age of onset, visual acuity, refraction, electrophysiology, autofluorescence, retinal appearance), and genotype\u2013phenotype correlation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>For 32 families, 26 unique pathogenic variants were identified; in <jats:italic>RP2<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a06, 21.9% of all families), <jats:italic>RPGR<\/jats:italic> exons 1\u201314 (<jats:italic>n<\/jats:italic>\u00a0=\u00a010, 43.75%), and <jats:italic>RPGR\u2010<\/jats:italic>ORF15 (<jats:italic>n<\/jats:italic>\u00a0=\u00a010, 34.3%). Three <jats:italic>RP2<\/jats:italic> and 8 <jats:italic>RPGR<\/jats:italic> exons 1\u201314 variants are novel, rare, and cosegregate. Thirty\u2010one percent of carrier females were significantly affected, with 18.5% of families initially classified as autosomal dominant. Of five Polynesian families, 80% had novel disease\u2010causing variants. One M\u0101ori family showed keratoconus segregating with an <jats:italic>ORF15<\/jats:italic> variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Significant disease was present in 31% of genetically proven female carriers, often leading to an erroneous presumption of the inheritance pattern. Pathogenic variants in 44% of the families were in exon 1\u201314 of <jats:italic>RPGR<\/jats:italic>, more frequent than usually described, which may inform the gene testing algorithm. Proving cosegregation in families for novel variants and identifying affected females and males translates to optimised clinical care and potential for gene therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ceo.14220","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T05:14:49Z","timestamp":1678252489000},"page":"300-312","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genotypic and phenotypic characterisation of <i>RP2<\/i>\u2010 and <i>RPGR<\/i>\u2010associated X\u2010linked inherited retinal dystrophy, including female manifestations"],"prefix":"10.1111","volume":"51","author":[{"given":"Shilpa E.","family":"Kuruvilla","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medical and Health Sciences, New Zealand National Eye Centre University of Auckland  Auckland New Zealand"},{"name":"Eye Department, Greenlane Clinical Centre Auckland District 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