{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T16:28:12Z","timestamp":1783441692984,"version":"3.54.6"},"reference-count":40,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korean Retina Foundation (KRS)","award":["RS-2024-00512384"],"award-info":[{"award-number":["RS-2024-00512384"]}]},{"name":"Korean ARPA-H Project through the Korean Health Industry Development Institute (KHIDI)","award":["RS-2024-00512384"],"award-info":[{"award-number":["RS-2024-00512384"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Senior-Loken syndrome (SLS) is a rare autosomal recessive renal\u2013retinal disease caused by mutations in 10 genes. This study aimed to review the ophthalmic findings, renal function, and genotypes of Korean SLS cases. Methods: We retrospectively reviewed 17 genetically confirmed SLS patients in Korea, including 9 newly identified cases and 8 previously reported. Comprehensive ophthalmologic evaluations and renal assessments were conducted. Genetic testing was performed using whole-genome sequencing (WGS), whole-exome sequencing (WES), or Sanger sequencing. Results: Among the 17 patients, patients with NPHP1 mutations were most common (35.3%), followed by those with NPHP4 (29.4%), IQCB1 (NPHP5, 29.4%), and SDCCAG8 (NPHP10, 5.9%) mutations. Patients with NPHP1 mutations showed retinitis pigmentosa (RP) sine pigmento and preserved central vision independent of renal deterioration. Patients with NPHP4 mutations showed early renal dysfunction. Two patients aged under 20 maintained relatively good visual function, but older individuals progressed to severe retinopathy. Patients with IQCB1 mutations were generally prone to early and severe retinal degeneration, typically manifesting as Leber congenital amaurosis (LCA) (three patients), while two patients exhibited milder RP sine pigmento with preserved central vision. Notably, two out of five (40.0%) maintained normal renal function at the time of diagnosis, and both had large deletions in IQCB1. The patient with SDCCAG8 mutation exhibited both end-stage renal disease and congenital blindness due to LCA. Wide-field fundus autofluorescence (AF) revealed perifoveal and peripapillary hypoAF with a perifoveal hyperAF in younger patients across genotypes. Patients under 20 years old showed relatively preserved central vision, regardless of the underlying genetic mutation. Conclusions: The clinical manifestation of renal and ocular impairment demonstrated heterogeneity among Korean SLS patients according to causative genes, and the severity of renal dysfunction and visual decline was not correlated. Therefore, simultaneous comprehensive evaluations of both renal and ocular function should be performed at the initial diagnosis to guide timely intervention and optimize long-term outcomes.<\/jats:p>","DOI":"10.3390\/genes16070835","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T12:09:53Z","timestamp":1752840593000},"page":"835","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical and Genetic Characteristics of Senior-Loken Syndrome Patients in Korea"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6585-7687","authenticated-orcid":false,"given":"Jae Ryong","family":"Song","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 136705, Republic of Korea"},{"name":"Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3799-1150","authenticated-orcid":false,"given":"Sangwon","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwangsic","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 136705, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoon Il","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4293-9641","authenticated-orcid":false,"given":"Yoon Jeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3692-7169","authenticated-orcid":false,"given":"Se Joon","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 136705, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.visres.2012.07.003","article-title":"Senior-L\u00f8ken syndrome: A syndromic form of retinal dystrophy associated with nephronophthisis","volume":"75","author":"Ronquillo","year":"2012","journal-title":"Vis. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"418","DOI":"10.7863\/jum.2007.26.3.418","article-title":"Senior-Loken syndrome","volume":"26","author":"Pretorius","year":"2007","journal-title":"J. Ultrasound Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/ng1520","article-title":"Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin","volume":"37","author":"Otto","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1681\/ASN.2008050456","article-title":"Nephronophthisis: Disease mechanisms of a ciliopathy","volume":"20","author":"Hildebrandt","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1542\/peds.94.1.111","article-title":"Senior-Loken syndrome: Revisited","volume":"94","author":"Warady","year":"1994","journal-title":"Pediatrics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1097\/IAE.0000000000003138","article-title":"Senior-L\u00f8ken syndrome: A case series and review of the renoretinal phenotype and advances of molecular diagnosis","volume":"41","author":"Yahalom","year":"2021","journal-title":"Retina"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e251","DOI":"10.1038\/emm.2016.63","article-title":"Targeted exome sequencing resolves allelic and the genetic heterogeneity in the genetic diagnosis of nephronophthisis-related ciliopathy","volume":"48","author":"Kang","year":"2016","journal-title":"Exp. Mol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s10633-008-9155-4","article-title":"ISCEV Standard for full-field clinical electroretinography (2008 update)","volume":"118","author":"Marmor","year":"2009","journal-title":"Doc. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10633-011-9296-8","article-title":"ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition)","volume":"124","author":"Hood","year":"2012","journal-title":"Doc. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10633-014-9473-7","article-title":"ISCEV Standard for full-field clinical electroretinography (2015 update)","volume":"130","author":"McCulloch","year":"2015","journal-title":"Doc. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10633-017-9621-y","article-title":"ISCEV guide to visual electrodiagnostic procedures","volume":"136","author":"Robson","year":"2018","journal-title":"Doc. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1111\/cge.13848","article-title":"Diagnostic yield and clinical utility of whole exome sequencing using an automated variant prioritization system, EVIDENCE","volume":"98","author":"Seo","year":"2020","journal-title":"Clin. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1093\/bioinformatics\/btv710","article-title":"Manta: Rapid detection of structural variants and indels for germline and cancer sequencing applications","volume":"32","author":"Chen","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1101\/gr.218032.116","article-title":"The Mobile Element Locator Tool (MELT): Population-scale mobile element discovery and biology","volume":"27","author":"Gardner","year":"2017","journal-title":"Genome Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4754","DOI":"10.1093\/bioinformatics\/btz431","article-title":"ExpansionHunter: A sequence-graph-based tool to analyze variation in short tandem repeat regions","volume":"35","author":"Dolzhenko","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"McLaren, W., Gil, L., Hunt, S.E., Riat, H.S., Ritchie, G.R., Thormann, A., Flicek, P., and Cunningham, F. (2016). The Ensembl Variant Effect Predictor. Genome Biol., 17.","DOI":"10.1186\/s13059-016-0974-4"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/s41467-020-20584-4","article-title":"AutoMap is a high performance homozygosity mapping tool using next-generation sequencing data","volume":"12","author":"Quinodoz","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1002\/humu.24107","article-title":"Specifications of the ACMG\/AMP standards and guidelines for mitochondrial DNA variant interpretation","volume":"41","author":"McCormick","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41436-019-0686-8","article-title":"Technical standards for the interpretation and reporting of constitutional copy-number variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)","volume":"22","author":"Riggs","year":"2020","journal-title":"Genet. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1093\/bioinformatics\/btm091","article-title":"Enhancements and modifications of primer design program Primer3","volume":"23","author":"Koressaar","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e115","DOI":"10.1093\/nar\/gks596","article-title":"Primer3\u2014New capabilities and interfaces","volume":"40","author":"Untergasser","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1001\/archophthalmol.2010.330","article-title":"Variations in NPHP5 in patients with nonsyndromic leber congenital amaurosis and Senior-Loken syndrome","volume":"129","author":"Stone","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1093\/hmg\/ddu738","article-title":"Nephrocystin proteins NPHP5 and Cep290 regulate BBSome integrity, ciliary trafficking and cargo delivery","volume":"24","author":"Barbelanne","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s00018-019-03181-7","article-title":"Requirement of NPHP5 in the hierarchical assembly of basal feet associated with basal bodies of primary cilia","volume":"77","author":"Hossain","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1681\/ASN.2010090965","article-title":"Retinal abnormalities characteristic of inherited renal disease","volume":"22","author":"Savige","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ajo.2023.03.025","article-title":"Pathogenic Variants in CEP290 or IQCB1 Cause Earlier-Onset Retinopathy in Senior-Loken Syndrome Compared to Those in INVS, NPHP3, or NPHP4","volume":"252","author":"Wang","year":"2023","journal-title":"Am. J. Ophthalmol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1566","DOI":"10.1002\/mgg3.1566","article-title":"Defective INPP5E distribution in NPHP1-related Senior-Loken syndrome","volume":"9","author":"Ning","year":"2021","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3368","DOI":"10.1093\/hmg\/ddn231","article-title":"Targeted disruption of Nphp1 causes male infertility due to defects in the later steps of sperm morphogenesis in mice","volume":"17","author":"Jiang","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e355","DOI":"10.1038\/cddis.2012.96","article-title":"Selective loss of RPGRIP1-dependent ciliary targeting of NPHP4, RPGR and SDCCAG8 underlies the degeneration of photoreceptor neurons","volume":"3","author":"Patil","year":"2012","journal-title":"Cell Death Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"18520","DOI":"10.1073\/pnas.0505774102","article-title":"Interaction of nephrocystin-4 and RPGRIP1 is disrupted by nephronophthisis or Leber congenital amaurosis-associated mutations","volume":"102","author":"Roepman","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1093\/hmg\/ddl107","article-title":"In-frame deletion in a novel centrosomal\/ciliary protein CEP290\/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse","volume":"15","author":"Chang","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1093\/hmg\/ddq494","article-title":"NPHP4 is necessary for normal photoreceptor ribbon synapse maintenance and outer segment formation, and for sperm development","volume":"20","author":"Won","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3400","DOI":"10.1096\/fj.201600511R","article-title":"Ciliopathy-associated IQCB1\/NPHP5 protein is required for mouse photoreceptor outer segment formation","volume":"30","author":"Ronquillo","year":"2016","journal-title":"FASEB J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1167\/iovs.10-5221","article-title":"IQCB1 mutations in patients with leber congenital amaurosis","volume":"52","author":"Koenekoop","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/ng.662","article-title":"Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy","volume":"42","author":"Otto","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1007\/s00417-023-06309-5","article-title":"Whole genome sequencing for inherited retinal diseases in the Korean National Project of Bio Big Data","volume":"262","author":"Oh","year":"2024","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e112","DOI":"10.1016\/j.jcjo.2021.01.010","article-title":"Senior-Loken syndrome secondary to IQCB1 mutation in association with retinitis pigmentosa","volume":"56","author":"Rishi","year":"2021","journal-title":"Can. J. Ophthalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1111\/j.1399-3046.2008.00942.x","article-title":"Outcomes of kidney transplantation in children with nephronophthisis: An analysis of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) Registry","volume":"12","author":"Hamiwka","year":"2008","journal-title":"Pediatr. Transpl."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/7\/835\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:11:44Z","timestamp":1760033504000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/7\/835"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,17]]},"references-count":40,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["genes16070835"],"URL":"https:\/\/doi.org\/10.3390\/genes16070835","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,17]]}}}