{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:58:38Z","timestamp":1790164718210,"version":"4.1.0"},"reference-count":31,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>RPE65-associated inherited retinal dystrophy (RPE65-IRD) is an early-onset retinal degeneration. The aim of this study was to describe the clinical features and natural course of this disease in a Chinese patient cohort with RPE65 biallelic variants. Thirty patients from 29 unrelated families with biallelic disease-causing RPE65 variants underwent full ophthalmic examinations. Thirteen were followed up over time. An additional 57 Chinese cases from 49 families were retrieved from the literature to analyze the relationship between best-corrected visual acuity (BCVA) and age. Our 30 patients presented age-dependent phenotypic characteristics. Multiple white dots were a clinical feature of young patients, while maculopathy, epiretinal membrane, and bone spicules were common in adult patients. Among the 84 patients, BCVA declined with age in a nonlinear, positive-acceleration relationship (p &lt; 0.001). All patients older than 40 years met the WHO standard for low vision. Longitudinal observation revealed a slower visual acuity loss in patients younger than 20 years than those in their third or fourth decade of life. Our study detailed the clinical features and natural course of disease in Chinese patients with RPE65-IRD. Our results indicated that these patients have a relatively stable BCVA in childhood and adolescence, but eyesight deteriorates rapidly in the third decade of life. These findings may facilitate the implementation of gene therapy in China.<\/jats:p>","DOI":"10.3390\/jcm10225229","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T09:19:21Z","timestamp":1636535961000},"page":"5229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Clinical Features and Natural History in a Cohort of Chinese Patients with RPE65-Associated Inherited Retinal Dystrophy"],"prefix":"10.3390","volume":"10","author":[{"given":"Jie","family":"Shi","sequence":"first","affiliation":[{"name":"Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[{"name":"Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Ping","family":"Hu","sequence":"additional","affiliation":[{"name":"Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Xie","sequence":"additional","affiliation":[{"name":"Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Bing","family":"Jin","sequence":"additional","affiliation":[{"name":"Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8734-4054","authenticated-orcid":false,"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.exer.2008.07.015","article-title":"Focus on molecules: RPE65, the visual cycle retinol isomerase","volume":"88","author":"Redmond","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Daich Varela, M., Cabral de Guimaraes, T.A., Georgiou, M., and Michaelides, M. (2021). Leber congenital amaurosis\/early-onset severe retinal dystrophy: Current management and clinical trials. Br. J. Ophthalmol.","DOI":"10.1136\/bjophthalmol-2020-318483"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"112","DOI":"10.12998\/wjcc.v3.i2.112","article-title":"Review and update on the molecular basis of Leber congenital amaurosis","volume":"3","author":"Zenteno","year":"2015","journal-title":"World J. Clin. Cases"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1136\/bjophthalmol-2016-309975","article-title":"Leber congenital amaurosis\/early-onset severe retinal dystrophy: Clinical features, molecular genetics and therapeutic interventions","volume":"101","author":"Kumaran","year":"2017","journal-title":"Br. J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/ejhg.2015.241","article-title":"Comprehensive genotyping reveals RPE65 as the most frequently mutated gene in Leber congenital amaurosis in Denmark","volume":"24","author":"Astuti","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e181","DOI":"10.1111\/aos.14181","article-title":"RPE65 mutation frequency and phenotypic variation according to exome sequencing in a tertiary centre for genetic eye diseases in China","volume":"98","author":"Li","year":"2020","journal-title":"Acta Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1136\/bjophthalmol-2019-314281","article-title":"Genetic and clinical findings in a Chinese cohort with Leber congenital amaurosis and early onset severe retinal dystrophy","volume":"104","author":"Xu","year":"2020","journal-title":"Br. J. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/s13023-021-01807-3","article-title":"Frequency and phenotypic characteristics of RPE65 mutations in the Chinese population","volume":"16","author":"Gao","year":"2021","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1097\/IAE.0000000000002681","article-title":"Longitudinal study of RPE65- associated inherited retinal degenerations","volume":"40","author":"Pierrache","year":"2020","journal-title":"Retina"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s00417-004-1020-x","article-title":"Longitudinal and cross-sectional study of patients with early-onset severe retinal dystrophy associated with RPE65 mutations","volume":"243","author":"Paunescu","year":"2005","journal-title":"Graefes. Arch. Clin. Exp. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ajo.2018.09.024","article-title":"The natural history of inherited retinal dystrophy due to biallelic mutations in the RPE65 Gene","volume":"199","author":"Chung","year":"2019","journal-title":"Am. J. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1136\/bjophthalmol-2015-308019","article-title":"Preserved visual function in retinal dystrophy due to hypomorphic RPE65 mutations","volume":"100","author":"Hull","year":"2016","journal-title":"Br. J. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5235","DOI":"10.1167\/iovs.07-1671","article-title":"A comprehensive clinical and biochemical functional study of a novel RPE65 hypomorphic mutation","volume":"49","author":"Lorenz","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0140-6736(17)31868-8","article-title":"Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: A randomised, controlled, open-label, phase 3 trial","volume":"390","author":"Russell","year":"2017","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13023-020-1304-1","article-title":"The effect of human gene therapy for RPE65-associated Leber\u2019s congenital amaurosis on visual function: A systematic review and meta-analysis","volume":"15","author":"Wang","year":"2020","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.cell.2018.03.021","article-title":"Gene therapy for retinal degeneration","volume":"173","author":"Apte","year":"2018","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1080\/14656566.2018.1448060","article-title":"Pharmacotherapy of retinal disease with visual cycle modulators","volume":"19","author":"Hussain","year":"2018","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_18","first-page":"204","article-title":"Seven novel variants expand the spectrum of RPE65-related Leber congenital amaurosis in the Chinese population","volume":"25","author":"Zhong","year":"2019","journal-title":"Mol. Vis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/gim.2014.138","article-title":"Genotype-phenotype correlation and mutation spectrum in a large cohort of patients with inherited retinal dystrophy revealed by next-generation sequencing","volume":"17","author":"Huang","year":"2015","journal-title":"Genet. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1167\/iovs.17-23312","article-title":"Comprehensive molecular screening in Chinese Usher Syndrome patients","volume":"59","author":"Sun","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","first-page":"744","article-title":"Novel RPE65 mutations associated with Leber congenital amaurosis in Chinese patients","volume":"18","author":"Xu","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1131","DOI":"10.1002\/mgg3.1131","article-title":"Application of targeted panel sequencing and whole exome sequencing for 76 Chinese families with retinitis pigmentosa","volume":"8","author":"Dan","year":"2020","journal-title":"Mol. Genet. Genomic. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mo, G., Ding, Q., Chen, Z., Li, Y., Yan, M., Bu, L., Song, Y., and Yin, G. (2014). A novel mutation in the RPE65 gene causing Leber congenital amaurosis and its transcriptional expression in vitro. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112400"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.4103\/0366-6999.218007","article-title":"A Gene Scan Study of RPE65 in Chinese Patients with Leber Congenital Amaurosis","volume":"130","author":"Liu","year":"2017","journal-title":"Chin. Med. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4158","DOI":"10.1167\/iovs.13-11672","article-title":"Next-generation sequencing-based molecular diagnosis of a Chinese patient cohort with autosomal recessive retinitis pigmentosa","volume":"54","author":"Fu","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3330","DOI":"10.1167\/iovs.18-23873","article-title":"A cross-sectional and longitudinal study of retinal sensitivity in RPE65-associated Leber Congenital Amaurosis","volume":"59","author":"Kumaran","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.ophtha.2010.09.005","article-title":"Fundus albipunctatus associated with compound heterozygous mutations in RPE65","volume":"118","author":"Schatz","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"46285","DOI":"10.1038\/srep46285","article-title":"Genetic and phenotypic characteristics of four Chinese families with fundus albipunctatus","volume":"7","author":"Yang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_29","first-page":"286","article-title":"Early onset flecked retinal dystrophy associated with new compound heterozygous RPE65 variants","volume":"24","author":"Katagiri","year":"2018","journal-title":"Mol. Vis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1167\/iovs.61.4.47","article-title":"Retinal structure in RPE65-associated retinal dystrophy","volume":"61","author":"Kumaran","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1136\/bjophthalmol-2018-311964","article-title":"Prevalence of cystoid macular oedema, epiretinal membrane and cataract in retinitis pigmentosa","volume":"103","author":"Liew","year":"2019","journal-title":"Br. J. Ophthalmol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/22\/5229\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:28:32Z","timestamp":1760167712000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/22\/5229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,10]]},"references-count":31,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["jcm10225229"],"URL":"https:\/\/doi.org\/10.3390\/jcm10225229","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,10]]}}}