{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T10:40:05Z","timestamp":1770979205229,"version":"3.50.1"},"reference-count":17,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T00:00:00Z","timestamp":1639440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Reported growth rates (GR) of atrophic lesions in Stargardt disease (STGD1) vary widely. In the present study, we report the longitudinal natural history of patients with confirmed biallelic ABCA4 mutations from five genotype groups: c.6079C&gt;T, c.[2588G&gt;C;5603A&gt;T], c.3113C&gt;T, c.5882G&gt;A and c.5603A&gt;T. Fundus autofluorescence (AF) 30\u00b0 \u00d7 30\u00b0 images were manually segmented for boundaries of definitely decreased autofluorescence (DDAF). The primary outcome was the effective radius GR across five genotype groups. The age of DDAF formation in each eye was calculated using the x-intercept of the DDAF effective radius against age. Discordance between age at DDAF formation and symptom onset was compared. A total of 75 eyes from 39 STGD1 patients (17 male [44%]; mean \u00b1 SD age 45 \u00b1 19 years; range 21\u201386) were recruited. Patients with c.3113C&gt;T or c.6079C&gt;T had a significantly faster effective radius GR at 0.17 mm\/year (95% CI 0.12 to 0.22; p &lt; 0.001 and 0.14 to 0.21; p &lt; 0.001) respectively, as compared to those patients harbouring c.5882G&gt;A at 0.06 mm\/year (95% CI 0.03\u20130.09), respectively. Future clinical trial design should consider the effect of genotype on the effective radius GR and the timing of DDAF formation relative to symptom onset.<\/jats:p>","DOI":"10.3390\/genes12121981","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T09:34:25Z","timestamp":1639474465000},"page":"1981","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Genotype-Specific Lesion Growth Rates in Stargardt Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Rachael C.","family":"Heath Jeffery","sequence":"first","affiliation":[{"name":"Centre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute), The University of Western Australia, Nedlands, WA 6009, Australia"},{"name":"Department of Ophthalmology, Royal Perth Hospital, Perth, WA 6000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3553-6457","authenticated-orcid":false,"given":"Jennifer A.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1913-5354","authenticated-orcid":false,"given":"Johnny","family":"Lo","sequence":"additional","affiliation":[{"name":"School of Science, Edith Cowan University, Joondalup, WA 6027, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina M.","family":"Lamey","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute), The University of Western Australia, Nedlands, WA 6009, Australia"},{"name":"Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terri L.","family":"McLaren","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute), The University of Western Australia, Nedlands, WA 6009, Australia"},{"name":"Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3262-0821","authenticated-orcid":false,"given":"Ian L.","family":"McAllister","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute), The University of Western Australia, Nedlands, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian J.","family":"Constable","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute), The University of Western Australia, Nedlands, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John N.","family":"De Roach","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute), The University of Western Australia, Nedlands, WA 6009, Australia"},{"name":"Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2809-9930","authenticated-orcid":false,"given":"Fred K.","family":"Chen","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute), The University of Western Australia, Nedlands, WA 6009, Australia"},{"name":"Department of Ophthalmology, Royal Perth Hospital, Perth, WA 6000, Australia"},{"name":"Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1080\/13816810.2021.1913610","article-title":"Inherited retinal diseases are the most common cause of blindness in the working-age population in Australia","volume":"42","author":"Mukhtar","year":"2021","journal-title":"Ophthalmic Genet."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Runhart, E.H., Dhooge, P., Meester-Smoor, M., Pas, J., Pott, J.W.R., van Leeuwen, R., Kroes, H.Y., Bergen, A.A., Jong-Hesse, Y., and Thiadens, A.A. (2021). Stargardt disease: Monitoring incidence and diagnostic trends in the Netherlands using a nationwide disease registry. Acta Ophthalmol., online ahead of print.","DOI":"10.1111\/aos.14996"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100005","DOI":"10.1016\/j.xops.2021.100005","article-title":"Atrophy Expansion Rates in Stargardt Disease Using Ultra-Widefield Fundus Autofluorescence","volume":"1","author":"Thompson","year":"2021","journal-title":"Ophthalmol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/ceo.13947","article-title":"Stargardt disease: Multimodal imaging: A review","volume":"49","author":"Chen","year":"2021","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1001\/jamaophthalmol.2013.572","article-title":"Square Root Transformation of Geographic Atrophy Area Measurements to Eliminate Dependence of Growth Rates on Baseline Lesion Measurements: A Reanalysis of Age-Related Eye Disease Study Report No. 26","volume":"131","author":"Feuer","year":"2013","journal-title":"JAMA Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1016\/j.ophtha.2019.05.015","article-title":"Natural History of Autosomal Recessive Stargardt Disease in Untreated Eyes: A Systematic Review and Meta-analysis of Study- and Individual-Level Data","volume":"126","author":"Shen","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1111\/ceo.12020","article-title":"Establishment and evolution of the Australian Inherited Retinal Disease Register and DNA Bank","volume":"41","author":"McLaren","year":"2013","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100861","DOI":"10.1016\/j.preteyeres.2020.100861","article-title":"Clinical spectrum, genetic complexity and therapeutic approaches for retinal disease caused by ABCA4 mutations","volume":"79","author":"Cremers","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1002\/humu.24100","article-title":"Functional analysis and classification of homozygous and hypomorphic ABCA4 variants associated with Stargardt macular degeneration","volume":"41","author":"Curtis","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5963","DOI":"10.1167\/iovs.16-20446","article-title":"The Effect on Retinal Structure and Function of 15 Specific ABCA4 Mutations: A Detailed Examination of 82 Hemizygous Patients","volume":"57","author":"Fakin","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/79994","article-title":"Biochemical defects in ABCR protein variants associated with human retinopathies","volume":"26","author":"Sun","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1097\/IAE.0000000000003227","article-title":"Classifying ABCA4 mutation severity using age-dependent ultra-widefield fundus autofluorescence-derived total lesion size","volume":"41","author":"Thompson","year":"2021","journal-title":"Retina"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1167\/iovs.17-23364","article-title":"Correlating the Expression and Functional Activity of ABCA4 Disease Variants With the Phenotype of Patients With Stargardt Disease","volume":"59","author":"Garces","year":"2018","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3220","DOI":"10.1093\/hmg\/ddv073","article-title":"Protein misfolding and the pathogenesis of ABCA4-associated retinal degenerations","volume":"24","author":"Zhang","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e28","DOI":"10.1016\/j.ophtha.2020.01.044","article-title":"Re: Shen et al.: Natural history of autosomal recessive Stargardt disease in untreated eyes: A systematic review and meta-analysis of study and individual level data (Ophthalmology. 2019;126:1288\u20131296)","volume":"127","author":"Kong","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1167\/tvst.9.11.12","article-title":"Retinal Boundary Segmentation in Stargardt Disease Optical Coherence Tomography Images Using Automated Deep Learning","volume":"9","author":"Kugelman","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1097\/IAE.0b013e3181e46af3","article-title":"Nidek MP1 is able to detect subtle decline in function in inherited and age-related atrophic macular disease with stable visual acuity","volume":"31","author":"Chen","year":"2011","journal-title":"Retina"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/12\/1981\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:47:18Z","timestamp":1760168838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/12\/1981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,14]]},"references-count":17,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["genes12121981"],"URL":"https:\/\/doi.org\/10.3390\/genes12121981","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,14]]}}}