{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T21:03:35Z","timestamp":1774559015764,"version":"3.50.1"},"reference-count":37,"publisher":"Proceedings of the National Academy of Sciences","issue":"27","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,7,5]]},"abstract":"<jats:p>Nanophthalmos is a rare disorder of eye development characterized by extreme hyperopia (farsightedness), with refractive error in the range of +8.00 to +25.00 diopters. Because the cornea and lens are normal in size and shape, hyperopia occurs because insufficient growth along the visual axis places these lensing components too close to the retina. Nanophthalmic eyes show considerable thickening of both the choroidal vascular bed and scleral coat, which provide nutritive and structural support for the retina. Thickening of these tissues is a general feature of axial hyperopia, whereas the opposite occurs in myopia. We have mapped recessive nanophthalmos to a unique locus at 11q23.3 and identified four independent mutations in<jats:italic>MFRP<\/jats:italic>, a gene that is selectively expressed in the eye and encodes a protein with homology to Tolloid proteases and the Wnt-binding domain of the Frizzled transmembrane receptors. This gene is not critical for retinal function, as patients entirely lacking<jats:italic>MFRP<\/jats:italic>can still have good refraction-corrected vision, produce clinically normal electro-retinograms, and show only modest anomalies in the dark adaptation of photoreceptors.<jats:italic>MFRP<\/jats:italic>appears primarily devoted to regulating axial length of the eye. It remains to be determined whether natural variation in its activity plays a role in common refractive errors.<\/jats:p>","DOI":"10.1073\/pnas.0501451102","type":"journal-article","created":{"date-parts":[[2005,6,24]],"date-time":"2005-06-24T00:38:58Z","timestamp":1119573538000},"page":"9553-9558","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":143,"title":["Extreme hyperopia is the result of null mutations in<i>MFRP<\/i>, which encodes a Frizzled-related protein"],"prefix":"10.1073","volume":"102","author":[{"given":"Olof H.","family":"Sundin","sequence":"first","affiliation":[{"name":"Laboratory of Developmental Genetics, Johns Hopkins Clinic for Hereditary Eye Diseases, Krieger Center for Pediatric Ophthalmology, Ocular Imaging and Low Vision Clinics, Wilmer Eye Institute, Department of Molecular Biology and Genetics, School of Medicine, and Department of Biostatistics, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21287; Department of Ophthalmology, University of Coimbra, 3000-033 Coimbra, Portugal; Instituto de Oftalmologia Dr. Gama Pinto, 1169..."}]},{"given":"Gregory S.","family":"Leppert","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Genetics, Johns Hopkins Clinic for Hereditary Eye Diseases, Krieger Center for Pediatric Ophthalmology, Ocular Imaging and Low Vision Clinics, Wilmer Eye Institute, Department of Molecular Biology and Genetics, School of Medicine, and Department of Biostatistics, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21287; Department of Ophthalmology, University of Coimbra, 3000-033 Coimbra, Portugal; Instituto de Oftalmologia Dr. Gama Pinto, 1169..."}]},{"given":"Eduardo D.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Genetics, Johns Hopkins Clinic for Hereditary Eye Diseases, Krieger Center for Pediatric Ophthalmology, Ocular Imaging and Low Vision Clinics, Wilmer Eye Institute, Department of Molecular Biology and Genetics, School of Medicine, and Department of Biostatistics, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21287; Department of Ophthalmology, University of Coimbra, 3000-033 Coimbra, Portugal; Instituto de Oftalmologia Dr. Gama Pinto, 1169..."}]},{"given":"Jun-Ming","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Genetics, Johns Hopkins Clinic for Hereditary Eye Diseases, Krieger Center for Pediatric Ophthalmology, Ocular Imaging and Low Vision Clinics, Wilmer Eye Institute, Department of Molecular Biology and Genetics, School of Medicine, and Department of Biostatistics, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21287; Department of Ophthalmology, University of Coimbra, 3000-033 Coimbra, Portugal; Instituto de Oftalmologia Dr. Gama Pinto, 1169..."}]},{"given":"Sharola","family":"Dharmaraj","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Genetics, Johns Hopkins Clinic for Hereditary Eye Diseases, Krieger Center for Pediatric Ophthalmology, Ocular Imaging and Low Vision Clinics, Wilmer Eye Institute, Department of Molecular Biology and Genetics, School of Medicine, and Department of Biostatistics, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21287; 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Department of Ophthalmology, University of Coimbra, 3000-033 Coimbra, Portugal; Instituto de Oftalmologia Dr. Gama Pinto, 1169..."}]},{"given":"Cameron F.","family":"Parsa","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Genetics, Johns Hopkins Clinic for Hereditary Eye Diseases, Krieger Center for Pediatric Ophthalmology, Ocular Imaging and Low Vision Clinics, Wilmer Eye Institute, Department of Molecular Biology and Genetics, School of Medicine, and Department of Biostatistics, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21287; Department of Ophthalmology, University of Coimbra, 3000-033 Coimbra, Portugal; Instituto de Oftalmologia Dr. Gama Pinto, 1169..."}]},{"given":"Elias I.","family":"Traboulsi","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Genetics, Johns Hopkins Clinic for Hereditary Eye Diseases, Krieger Center for Pediatric Ophthalmology, Ocular Imaging and Low Vision Clinics, Wilmer Eye Institute, Department of Molecular Biology and Genetics, School of Medicine, and Department of Biostatistics, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21287; Department of Ophthalmology, University of Coimbra, 3000-033 Coimbra, Portugal; Instituto de Oftalmologia Dr. Gama Pinto, 1169..."}]},{"given":"Karl W.","family":"Broman","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Genetics, Johns Hopkins Clinic for Hereditary Eye Diseases, Krieger Center for Pediatric Ophthalmology, Ocular Imaging and Low Vision Clinics, Wilmer Eye Institute, Department of Molecular Biology and Genetics, School of Medicine, and Department of Biostatistics, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21287; Department of Ophthalmology, University of Coimbra, 3000-033 Coimbra, Portugal; Instituto de Oftalmologia Dr. Gama Pinto, 1169..."}]},{"given":"Cathy","family":"DiBernardo","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Genetics, Johns Hopkins Clinic for Hereditary Eye Diseases, Krieger Center for Pediatric Ophthalmology, Ocular Imaging and Low Vision Clinics, Wilmer Eye Institute, Department of Molecular Biology and Genetics, School of Medicine, and Department of Biostatistics, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21287; 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