{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:40:22Z","timestamp":1791049222633,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Funds of China","award":["81970837"],"award-info":[{"award-number":["81970837"]}]},{"name":"National Natural Science Funds of China","award":["202102010271"],"award-info":[{"award-number":["202102010271"]}]},{"name":"Science and Technology Planning Projects of Guangzhou","award":["81970837"],"award-info":[{"award-number":["81970837"]}]},{"name":"Science and Technology Planning Projects of Guangzhou","award":["202102010271"],"award-info":[{"award-number":["202102010271"]}]},{"name":"Fundamental Research Funds of the State Key Laboratory of Ophthalmology","award":["81970837"],"award-info":[{"award-number":["81970837"]}]},{"name":"Fundamental Research Funds of the State Key Laboratory of Ophthalmology","award":["202102010271"],"award-info":[{"award-number":["202102010271"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Variants in FDXR reportedly cause autosomal recessive auditory neuropathy and optic atrophy, expanding to retinal dystrophy. This study aimed to further clarify associated phenotypes. FDXR variants were selected from our in-house whole-exome sequencing dataset of 6397 families with different eye conditions. The clinical data of the identified patients were summarized. Biallelic pathogenic or likely pathogenic FDXR variants were identified in 11 unrelated patients, including 14 missense variants of which 10 were novel. Fundus observation showed complete optic disc pallor, silver wiring or severe attenuation of retinal vessels, and varying degrees of generalized retinal degeneration. Before the detection of FDXR variants, four patients were clinically diagnosed as congenital amaurosis due to the presence of nystagmus a few months after birth, while seven were diagnosed as early-onset severe retinal dystrophy due to the presence of nyctalopia and\/or poor vision in early childhood. Biallelic FDXR variants are a frequent cause of congenital or early-onset severe retinal dystrophy, especially for patients with severe optic atrophy and retinal dystrophy in early childhood.<\/jats:p>","DOI":"10.3390\/genes14040952","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T04:01:23Z","timestamp":1682308883000},"page":"952","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["FDXR-Associated Oculopathy: Congenital Amaurosis and Early-Onset Severe Retinal Dystrophy as Common Presenting Features in a Chinese Population"],"prefix":"10.3390","volume":"14","author":[{"given":"Shutong","family":"Yi","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, 54 Xianlie Road, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, 54 Xianlie Road, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Yi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, 54 Xianlie Road, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingwei","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, 54 Xianlie Road, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, 54 Xianlie Road, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Ouyang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, 54 Xianlie Road, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqiang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, 54 Xianlie Road, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueshan","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, 54 Xianlie Road, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenmin","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, 54 Xianlie Road, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panfeng","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, 54 Xianlie Road, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7508-848X","authenticated-orcid":false,"given":"Qingjiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, 54 Xianlie Road, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.ajhg.2017.09.007","article-title":"FDXR Mutations Cause Sensorial Neuropathies and Expand the Spectrum of Mitochondrial Fe-S-Synthesis Diseases","volume":"101","author":"Paul","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s00239-017-9821-9","article-title":"Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme","volume":"85","author":"Hanukoglu","year":"2017","journal-title":"J. Mol. Evol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7104","DOI":"10.1073\/pnas.85.19.7104","article-title":"Human adrenodoxin reductase: Two mRNAs encoded by a single gene on chromosome 17cen----q25 are expressed in steroidogenic tissues","volume":"85","author":"Solish","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.omtm.2020.05.021","article-title":"Systemic Delivery of AAV-Fdxr Mitigates the Phenotypes of Mitochondrial Disorders in Fdxr Mutant Mice","volume":"18","author":"Yang","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1167\/iovs.62.6.2","article-title":"Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature","volume":"62","author":"Jurkute","year":"2021","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/brain\/awac395","article-title":"The top 10 most frequently involved genes in hereditary optic neuropathies in 2186 probands","volume":"146","author":"Rocatcher","year":"2023","journal-title":"Brain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/humu.24160","article-title":"Expanding the clinical and genetic spectrum of FDXR deficiency by functional validation of variants of uncertain significance","volume":"42","author":"Stenton","year":"2021","journal-title":"Hum. Mutat."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1002\/jdn.10104","article-title":"Report of a case with ferredoxin reductase (FDXR) gene variants in a Chinese boy exhibiting hearing loss, visual impairment, and motor retardation","volume":"81","author":"Yang","year":"2021","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1002\/humu.24181","article-title":"Genomic variants causing mitochondrial dysfunction are common in hereditary lower motor neuron disease","volume":"42","author":"Keller","year":"2021","journal-title":"Hum. Mutat."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1038\/s10038-018-0515-y","article-title":"Biallelic mutations in FDXR cause neurodegeneration associated with inflammation","volume":"63","author":"Slone","year":"2018","journal-title":"J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4937","DOI":"10.1093\/hmg\/ddx377","article-title":"Biallelic mutations in the ferredoxin reductase gene cause novel mitochondriopathy with optic atrophy","volume":"26","author":"Peng","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1056\/NEJMc1812033","article-title":"Reanalysis of Clinical Exome Sequencing Data","volume":"380","author":"Liu","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.18240\/ijo.2021.11.22","article-title":"Novel biallelic compound heterozygous mutations in FDXR cause optic atrophy in a young female patient: A case report","volume":"14","author":"Song","year":"2021","journal-title":"Int. J. Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4351","DOI":"10.1167\/iovs.13-11606","article-title":"Comprehensive mutation analysis by whole-exome sequencing in 41 Chinese families with Leber congenital amaurosis","volume":"54","author":"Chen","year":"2013","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/s41419-020-2637-3","article-title":"Integrated analysis of the molecular pathogenesis of FDXR-associated disease","volume":"11","author":"Slone","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1038\/ng.2361","article-title":"NMNAT1 mutations cause Leber congenital amaurosis","volume":"44","author":"Falk","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.braindev.2020.07.003","article-title":"Novel compound heterozygous ACO2 mutations in an infant with progressive encephalopathy: A newly identified neurometabolic syndrome","volume":"42","author":"Park","year":"2020","journal-title":"Brain Dev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1080\/13816810.2018.1502788","article-title":"A novel variant in IDH3A identified in a case with Leber congenital amaurosis accompanied by macular pseudocoloboma","volume":"39","author":"Sun","year":"2018","journal-title":"Ophthalmic Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"107846","DOI":"10.1016\/j.exer.2019.107846","article-title":"Pathogenicity discrimination and genetic test reference for CRX variants based on genotype-phenotype analysis","volume":"189","author":"Yi","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1167\/iovs.63.5.28","article-title":"Different Phenotypes Represent Advancing Stages of ABCA4-Associated Retinopathy: A Longitudinal Study of 212 Chinese Families From a Tertiary Center","volume":"63","author":"Wang","year":"2022","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ajo.2020.10.006","article-title":"Clinical and Genetic Analysis of 63 Families Demonstrating Early and Advanced Characteristic Fundus as the Signature of CRB1 Mutations","volume":"223","author":"Wang","year":"2021","journal-title":"Am. J. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e50260","DOI":"10.7554\/eLife.50260","article-title":"Degradation of engulfed mitochondria is rate-limiting in Optineurin-mediated mitophagy in neurons","volume":"9","author":"Evans","year":"2020","journal-title":"Elife"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Welch, B.M., Keil, A.P., van \u2018t Erve, T.J., Deterding, L.J., Williams, J.G., Lih, F.B., Cantonwine, D.E., McElrath, T.F., and Ferguson, K.K. (2020). Longitudinal profiles of plasma eicosanoids during pregnancy and size for gestational age at delivery: A nested case-control study. PLoS Med., 17.","DOI":"10.1371\/journal.pmed.1003271"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s12015-017-9771-z","article-title":"New Challenge: Mitochondrial Epigenetics?","volume":"14","author":"Stimpfel","year":"2018","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/BF02721213","article-title":"Ueber Retinitis pigmentosa und angeborene Amaurose","volume":"15","author":"Leber","year":"1869","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1159\/000105710","article-title":"Diagnostic and prognostic importance of the electroretinogram in tapetoretinal degeneration with reduction of the visual field and hemeralopia","volume":"14","author":"Franceschetti","year":"1954","journal-title":"Confin. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"108637","DOI":"10.1016\/j.exer.2021.108637","article-title":"Novel variants in GUCY2D causing retinopathy and the genotype-phenotype correlation","volume":"208","author":"Yi","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_28","first-page":"821","article-title":"Spectrum, frequency, and genotype-phenotype of mutations in SPATA7","volume":"25","author":"Xiao","year":"2019","journal-title":"Mol. Vis."},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1038\/s41433-021-01853-y","article-title":"Clinical features and genetic spectrum of NMNAT1-associated retinal degeneration","volume":"36","author":"Yi","year":"2021","journal-title":"Eye"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1001\/archopht.122.7.1029","article-title":"The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations","volume":"122","author":"Dharmaraj","year":"2004","journal-title":"Arch. Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wang, J., Li, S., Jiang, Y., Wang, Y., Ouyang, J., Yi, Z., Sun, W., Jia, X., Xiao, X., and Wang, P. (2023). Pathogenic variants in CEP290 or IQCB1 cause earlier onset retinopathy in Senior-Loken syndrome compared to those in INVS, NPHP3, or NPHP4. Am. J. Ophthalmol.","DOI":"10.1016\/j.ajo.2023.03.025"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1136\/jmedgenet-2018-105709","article-title":"Biallelic mutations in USP45, encoding a deubiquitinating enzyme, are associated with Leber congenital amaurosis","volume":"56","author":"Yi","year":"2019","journal-title":"J. Med. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1080\/14737175.2020.1821654","article-title":"Emerging therapies in Friedreich\u2019s Ataxia","volume":"20","author":"Zesiewicz","year":"2020","journal-title":"Expert Rev. Neurother."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/4\/952\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:21:02Z","timestamp":1760124062000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/4\/952"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,21]]},"references-count":34,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["genes14040952"],"URL":"https:\/\/doi.org\/10.3390\/genes14040952","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,21]]}}}