{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T16:47:17Z","timestamp":1775926037249,"version":"3.50.1"},"reference-count":107,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T00:00:00Z","timestamp":1735344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute of the National Institutes of Health","doi-asserted-by":"publisher","award":["R00EY027460"],"award-info":[{"award-number":["R00EY027460"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute of the National Institutes of Health","doi-asserted-by":"publisher","award":["US4GM104938"],"award-info":[{"award-number":["US4GM104938"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute of the National Institutes of Health","doi-asserted-by":"publisher","award":["P30EY027125"],"award-info":[{"award-number":["P30EY027125"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"VitreoRetinal Surgery Foundation","award":["R00EY027460"],"award-info":[{"award-number":["R00EY027460"]}]},{"name":"VitreoRetinal Surgery Foundation","award":["US4GM104938"],"award-info":[{"award-number":["US4GM104938"]}]},{"name":"VitreoRetinal Surgery Foundation","award":["P30EY027125"],"award-info":[{"award-number":["P30EY027125"]}]},{"DOI":"10.13039\/100000053","name":"NIH","doi-asserted-by":"publisher","award":["R00EY027460"],"award-info":[{"award-number":["R00EY027460"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"NIH","doi-asserted-by":"publisher","award":["US4GM104938"],"award-info":[{"award-number":["US4GM104938"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"NIH","doi-asserted-by":"publisher","award":["P30EY027125"],"award-info":[{"award-number":["P30EY027125"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Inherited retinal diseases (IRDs) represent a diverse group of genetic disorders characterized by degeneration of the retina, leading to visual impairment and blindness. IRDs are heterogeneous, sharing common clinical features that can be difficult to diagnose without knowing the genetic basis of the disease. To improve diagnostic accuracy and advance understanding of disease mechanisms, genetic testing was performed for 103 unrelated patients with an IRD at a single clinical site between 30 August 2022 and 5 February 2024. Methods: Informed consent was obtained before buccal samples were collected for panel-based sequencing at BluePrint Genetics (BpG), sponsored by the Foundation Fighting Blindness MyRetina Tracker program. A retina specialist performed standard visit assessments, including visual acuity (Snellen chart), slit lamp examination, fundus photography (Optos\u00ae, Dunfermline, UK), and spectral-domain optical coherence tomography (SD-OCT; Zeiss). Results: From 103 patients, genetic findings were reported for 70 individuals. Among these included 20 novel variants. Conclusions: These results clarify and confirm clinical diagnoses, aid in counseling patients on prognosis and family planning, and guide treatment options. This study not only holds promise for affected individuals but also expands the mutation spectrum to guide understanding of IRD.<\/jats:p>","DOI":"10.3390\/genes16010032","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T12:37:19Z","timestamp":1735648639000},"page":"32","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Expanding the Mutation Spectrum for Inherited Retinal Diseases"],"prefix":"10.3390","volume":"16","author":[{"given":"Jacob","family":"Lynn","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73114, USA"},{"name":"Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel J.","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73114, USA"},{"name":"Dean McGee Eye Institute, Oklahoma City, OK 73140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace K.","family":"Trigler","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6453-4165","authenticated-orcid":false,"given":"Ronald","family":"Kingsley","sequence":"additional","affiliation":[{"name":"Dean McGee Eye Institute, Oklahoma City, OK 73140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Razek G.","family":"Coussa","sequence":"additional","affiliation":[{"name":"Dean McGee Eye Institute, Oklahoma City, OK 73140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4537-6445","authenticated-orcid":false,"given":"Lea D.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73114, USA"},{"name":"Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73114, USA"},{"name":"Dean McGee Eye Institute, Oklahoma City, OK 73140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1136\/jmg.21.6.421","article-title":"A study of retinitis pigmentosa in the City of Birmingham. II Clinical and genetic heterogeneity","volume":"21","author":"Bundey","year":"1984","journal-title":"J. Med. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/ajmg.1320120107","article-title":"Genetic aspects of retinitis pigmentosa in China","volume":"12","author":"Hu","year":"1982","journal-title":"Am. J. Med. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/1098-1004(2001)17:1<42::AID-HUMU5>3.0.CO;2-K","article-title":"Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies","volume":"17","author":"Sohocki","year":"2001","journal-title":"Hum. Mutat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1016\/j.ophtha.2017.04.008","article-title":"Clinically Focused Molecular Investigation of 1000 Consecutive Families with Inherited Retinal Disease","volume":"124","author":"Stone","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/cge.12203","article-title":"Genes and mutations causing retinitis pigmentosa","volume":"84","author":"Daiger","year":"2013","journal-title":"Clin. Genet."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41434-020-0168-2","article-title":"Retinal gene therapy: An eye-opener of the 21st century","volume":"28","author":"Askou","year":"2021","journal-title":"Gene Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e1281","DOI":"10.1111\/aos.14807","article-title":"Shortening the Early Treatment Diabetic Retinopathy Study visual acuity test utilizing a novel computer software: Reproducibility in control and patient eyes","volume":"99","author":"Cohen","year":"2021","journal-title":"Acta Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e70","DOI":"10.1136\/jmg.2006.044511","article-title":"New VMD2 gene mutations identified in patients affected by Best vitelliform macular dystrophy","volume":"44","author":"Marchant","year":"2007","journal-title":"J. Med. Genet."},{"key":"ref_10","first-page":"1594","article-title":"Screening for BEST1 gene mutations in Chinese patients with bestrophinopathy","volume":"20","author":"Tian","year":"2014","journal-title":"Mol. Vis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s004390050972","article-title":"The mutation spectrum of the bestrophin protein--functional implications","volume":"104","author":"Bakall","year":"1999","journal-title":"Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ji, C., Li, Y., Kittredge, A., Hopiavuori, A., Ward, N., Yao, P., Fukuda, Y., Zhang, Y., Tsang, S.H., and Yang, T. (2019). Investigation and Restoration of BEST1 Activity in Patient-derived RPEs with Dominant Mutations. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-54892-7"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1186\/s12967-019-2080-3","article-title":"Pathogenicity of new BEST1 variants identified in Italian patients with best vitelliform macular dystrophy assessed by computational structural biology","volume":"17","author":"Frecer","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1001\/archophthalmol.2009.148","article-title":"Phenotypic variability due to a novel Glu292Lys variation in exon 8 of the BEST1 gene causing best macular dystrophy","volume":"127","author":"Sohn","year":"2009","journal-title":"Arch. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1111\/aos.14218","article-title":"Inherited retinal disease in Norway\u2014A characterization of current clinical and genetic knowledge","volume":"98","author":"Holtan","year":"2020","journal-title":"Acta Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1159\/000444681","article-title":"Novel BEST1 Mutations and Special Clinical Features of Best Vitelliform Macular Dystrophy","volume":"56","author":"Liu","year":"2016","journal-title":"Ophthalmic Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhu, J., Stephenson, K.A.J., Dockery, A., Turner, J., O\u2019Byrne, J.J., Fitzsimon, S., Farrar, G.J., Flitcroft, D.I., and Keegan, D.J. (2022). Electrophysiology-Guided Genetic Characterisation Maximises Molecular Diagnosis in an Irish Paediatric Inherited Retinal Degeneration Population. Genes, 13.","DOI":"10.3390\/genes13040615"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/humu.23903","article-title":"A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC)","volume":"41","author":"Sharon","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1002\/humu.24064","article-title":"Genetic architecture of inherited retinal degeneration in Germany: A large cohort study from a single diagnostic center over a 9-year period","volume":"41","author":"Weisschuh","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_20","first-page":"1009","article-title":"[Autosomal recessive bestrophinopathy (ARB): A clinical and molecular description of two patients at childhood]","volume":"229","author":"Preising","year":"2012","journal-title":"Klin. Monbl Augenheilkd."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1002\/humu.9189","article-title":"Ten novel mutations in VMD2 associated with Best macular dystrophy (BMD)","volume":"22","author":"Mohr","year":"2003","journal-title":"Hum. Mutat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/ng935","article-title":"Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome","volume":"31","author":"Mykytyn","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1086\/346172","article-title":"Evaluation of complex inheritance involving the most common Bardet-Biedl syndrome locus (BBS1)","volume":"72","author":"Mykytyn","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1086\/375178","article-title":"Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non-Mendelian Bardet-Biedl syndrome","volume":"72","author":"Beales","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1093\/hmg\/ddg188","article-title":"Heterozygous mutations in BBS1, BBS2 and BBS6 have a potential epistatic effect on Bardet-Biedl patients with two mutations at a second BBS locus","volume":"12","author":"Badano","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.visres.2012.08.005","article-title":"Phenotypic expression of Bardet-Biedl syndrome in patients homozygous for the common M390R mutation in the BBS1 gene","volume":"75","author":"Cox","year":"2012","journal-title":"Vis. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Bravo-Gil, N., M\u00e9ndez-Vidal, C., Romero-P\u00e9rez, L., Gonz\u00e1lez-del Pozo, M., Rodr\u00edguez-de la R\u00faa, E., Dopazo, J., Borrego, S., and Anti\u00f1olo, G. (2016). Improving the management of Inherited Retinal Dystrophies by targeted sequencing of a population-specific gene panel. Sci. Rep., 6.","DOI":"10.1038\/srep23910"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Jespersgaard, C., Fang, M., Bertelsen, M., Dang, X., Jensen, H., Chen, Y., Bech, N., Dai, L., Rosenberg, T., and Zhang, J. (2019). Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-38007-2"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1136\/jmedgenet-2012-100847","article-title":"A paradigm shift in the delivery of services for diagnosis of inherited retinal disease","volume":"49","author":"Mullaney","year":"2012","journal-title":"J. Med. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1001\/archophthalmol.2012.2434","article-title":"BBS1 mutations in a wide spectrum of phenotypes ranging from nonsyndromic retinitis pigmentosa to Bardet-Biedl syndrome","volume":"130","author":"Koenekoop","year":"2012","journal-title":"Arch. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wang, X., Feng, Y., Li, J., Zhang, W., Wang, J., Lewis, R.A., and Wong, L.J. (2016). Retinal Diseases Caused by Mutations in Genes Not Specifically Associated with the Clinical Diagnosis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165405"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"19422","DOI":"10.1073\/pnas.0708571104","article-title":"A knockin mouse model of the Bardet-Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity","volume":"104","author":"Davis","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1016\/j.bbadis.2011.07.006","article-title":"Molecular recruitment as a basis for negative dominant inheritance? propagation of misfolding in oligomers of IMPDH1, the mutated enzyme in the RP10 form of retinitis pigmentosa","volume":"1812","author":"Wang","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/gim.2015.127","article-title":"Expanding the clinical, allelic, and locus heterogeneity of retinal dystrophies","volume":"18","author":"Patel","year":"2016","journal-title":"Genet. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1001\/archophthalmol.2012.89","article-title":"Genotype-phenotype correlations in Bardet-Biedl syndrome","volume":"130","author":"Daniels","year":"2012","journal-title":"Arch. Ophthalmol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Nasser, F., Kohl, S., Kurtenbach, A., Kempf, M., Biskup, S., Zuleger, T., Haack, T.B., Weisschuh, N., Stingl, K., and Zrenner, E. (2022). Ophthalmic and Genetic Features of Bardet Biedl Syndrome in a German Cohort. Genes, 13.","DOI":"10.3390\/genes13071218"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1007\/s10384-018-0591-8","article-title":"Clinical characteristics of a Japanese patient with Bardet-Biedl syndrome caused by BBS10 mutations","volume":"62","author":"Kurata","year":"2018","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.visres.2007.08.024","article-title":"Retinal morphology in patients with BBS1 and BBS10 related Bardet-Biedl Syndrome evaluated by Fourier-domain optical coherence tomography","volume":"48","author":"Gerth","year":"2008","journal-title":"Vis. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1016\/j.ophtha.2010.01.040","article-title":"Mutations in the EYS gene account for approximately 5% of autosomal recessive retinitis pigmentosa and cause a fairly homogeneous phenotype","volume":"117","author":"Littink","year":"2010","journal-title":"Ophthalmology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ajhg.2016.12.003","article-title":"Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease","volume":"100","author":"Carss","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1167\/iovs.18-25531","article-title":"Extending the Spectrum of EYS-Associated Retinal Disease to Macular Dystrophy","volume":"60","author":"Pierrache","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1186\/s13023-021-01843-z","article-title":"Dissecting the role of EYS in retinal degeneration: Clinical and molecular aspects and its implications for future therapy","volume":"16","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Neubauer, J., Hahn, L., Birtel, J., Boon, C.J.F., Charbel Issa, P., and Fischer, M.D. (2022). GUCY2D-Related Retinal Dystrophy with Autosomal Dominant Inheritance-A Multicenter Case Series and Review of Reported Data. Genes, 13.","DOI":"10.3390\/genes13020313"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1167\/iovs.16-20413","article-title":"Postretinal Structure and Function in Severe Congenital Photoreceptor Blindness Caused by Mutations in the GUCY2D Gene","volume":"58","author":"Aguirre","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1167\/tvst.9.6.2","article-title":"Clinical and Genetic Characteristics of 15 Affected Patients From 12 Japanese Families with GUCY2D-Associated Retinal Disorder","volume":"9","author":"Liu","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5015","DOI":"10.1167\/iovs.08-1901","article-title":"Mutation analysis identifies GUCY2D as the major gene responsible for autosomal dominant progressive cone degeneration","volume":"49","author":"Kitiratschky","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s10633-023-09954-7","article-title":"A natural history study of autosomal dominant GUCY2D-associated cone-rod dystrophy","volume":"147","author":"Scopelliti","year":"2023","journal-title":"Doc. Ophthalmol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1167\/iovs.63.8.19","article-title":"Delineating the Clinical Phenotype of Patients With the c.629C&gt;G, p.Pro210Arg Mutation in Peripherin-2","volume":"63","author":"Conley","year":"2022","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_49","first-page":"326","article-title":"Novel variants identified with next-generation sequencing in Polish patients with cone-rod dystrophy","volume":"24","author":"Wawrocka","year":"2018","journal-title":"Mol. Vis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.ajo.2008.09.007","article-title":"Phenotypic variability and long-term follow-up of patients with known and novel PRPH2\/RDS gene mutations","volume":"147","author":"Renner","year":"2009","journal-title":"Am. J. Ophthalmol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1002\/humu.24065","article-title":"Genotype-phenotype associations in a large PRPH2-related retinopathy cohort","volume":"41","author":"Reeves","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Oishi, A., Fujinami, K., Mawatari, G., Naoi, N., Ikeda, Y., Ueno, S., Kuniyoshi, K., Hayashi, T., Kondo, H., and Mizota, A. (2021). Genetic and Phenotypic Landscape of PRPH2-Associated Retinal Dystrophy in Japan. Genes, 12.","DOI":"10.3390\/genes12111817"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.oret.2022.06.017","article-title":"Longitudinal Analysis of Functional and Structural Outcome Measures in PRPH2-Associated Retinal Dystrophy","volume":"7","author":"Thompson","year":"2023","journal-title":"Ophthalmol. Retin."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.oret.2023.05.010","article-title":"Analysis of the Outer Retinal Bands in ABCA4 and PRPH2-Associated Retinopathy using OCT","volume":"8","author":"Lo","year":"2024","journal-title":"Ophthalmol. Retin."},{"key":"ref_55","first-page":"80","article-title":"Identification of novel rhodopsin mutations responsible for retinitis pigmentosa: Implications for the structure and function of rhodopsin","volume":"53","author":"Macke","year":"1993","journal-title":"Am. J. Hum. Genet."},{"key":"ref_56","first-page":"e38","article-title":"Prevalence of Rhodopsin mutations in autosomal dominant Retinitis Pigmentosa in Spain: Clinical and analytical review in 200 families","volume":"93","author":"Corton","year":"2015","journal-title":"Acta Ophthalmol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6481","DOI":"10.1073\/pnas.88.15.6481","article-title":"Rhodopsin mutations in autosomal dominant retinitis pigmentosa","volume":"88","author":"Sung","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.exer.2015.09.013","article-title":"Nonsense mutations in the rhodopsin gene that give rise to mild phenotypes trigger mRNA degradation in human cells by nonsense-mediated decay","volume":"145","author":"Wensel","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Lynn, J., Raney, A., Britton, N., Ramoin, J., Yang, R.W., Radojevic, B., McClard, C.K., Kingsley, R., Coussa, R.G., and Bennett, L.D. (2022). Genetic Diagnosis for 64 Patients with Inherited Retinal Disease. Genes, 14.","DOI":"10.3390\/genes14010074"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/humu.1160","article-title":"Identification of novel RP2 mutations in a subset of X-linked retinitis pigmentosa families and prediction of new domains","volume":"18","author":"Miano","year":"2001","journal-title":"Hum. Mutat."},{"key":"ref_61","first-page":"413","article-title":"RP2-associated X-linked Retinopathy: Clinical Findings, Molecular Genetics, and Natural History in a Large Cohort of Female Carriers","volume":"130","author":"Georgiou","year":"2023","journal-title":"Am. J. Ophthalmol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ajo.2023.02.002","article-title":"Static Perimetry in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) Study: Assessment Through 2 Years","volume":"250","author":"Duncan","year":"2023","journal-title":"Am. J. Ophthalmol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1167\/iovs.63.3.17","article-title":"The RUSH2A Study: Dark-Adapted Visual Fields in Patients With Retinal Degeneration Associated With Biallelic Variants in the USH2A Gene","volume":"63","author":"Birch","year":"2022","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ajo.2022.08.013","article-title":"Baseline Microperimetry and OCT in the RUSH2A Study: Structure-Function Association and Correlation With Disease Severity","volume":"244","author":"Lad","year":"2022","journal-title":"Am. J. Ophthalmol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1136\/bjophthalmol-2019-315786","article-title":"USH2A variants in Chinese patients with Usher syndrome type II and non-syndromic retinitis pigmentosa","volume":"105","author":"Zhu","year":"2021","journal-title":"Br. J. Ophthalmol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/j.ophtha.2016.01.021","article-title":"Visual Prognosis in USH2A-Associated Retinitis Pigmentosa Is Worse for Patients with Usher Syndrome Type IIa Than for Those with Nonsyndromic Retinitis Pigmentosa","volume":"123","author":"Pierrache","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1038\/ejhg.2015.54","article-title":"Partial USH2A deletions contribute to Usher syndrome in Denmark","volume":"23","author":"Dad","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1038\/ejhg.2014.283","article-title":"A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants","volume":"23","author":"Lenassi","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1002\/humu.22608","article-title":"Enrichment of LOVD-USHbases with 152 USH2A genotypes defines an extensive mutational spectrum and highlights missense hotspots","volume":"35","author":"Baux","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1136\/jmg.2009.075143","article-title":"Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa","volume":"47","author":"McGee","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1089\/gte.2007.0107","article-title":"Four USH2A founder mutations underlie the majority of Usher syndrome type 2 cases among non-Ashkenazi Jews","volume":"12","author":"Auslender","year":"2008","journal-title":"Genet. Test."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/sj.ejhg.5200491","article-title":"Identification of novel USH2A mutations: Implications for the structure of USH2A protein","volume":"8","author":"Dreyer","year":"2000","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1086\/302855","article-title":"Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa","volume":"66","author":"Weston","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/(SICI)1098-1004(200004)15:4<388::AID-HUMU27>3.0.CO;2-N","article-title":"Three novel mutations and twelve polymorphisms identified in the USH2A gene in Israeli USH2 families","volume":"15","author":"Adato","year":"2000","journal-title":"Hum. Mutat."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5918","DOI":"10.1038\/s41467-020-19669-x","article-title":"Inferring the molecular and phenotypic impact of amino acid variants with MutPred2","volume":"11","author":"Pejaver","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Biswas, P., Villanueva, A.L., Soto-Hermida, A., Duncan, J.L., Matsui, H., Borooah, S., Kurmanov, B., Richard, G., Khan, S.Y., and Branham, K. (2021). Deciphering the genetic architecture and ethnographic distribution of IRD in three ethnic populations by whole genome sequence analysis. PLoS Genet., 17.","DOI":"10.1371\/journal.pgen.1009848"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"D497","DOI":"10.1093\/nar\/gkab975","article-title":"The Eukaryotic Linear Motif resource: 2022 release","volume":"50","author":"Kumar","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_78","first-page":"3925","article-title":"A high association with cone dystrophy in Fundus albipunctatus caused by mutations of the RDH5 gene","volume":"41","author":"Nakamura","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Yang, G., Liu, Z., Xie, S., Li, C., Lv, L., Zhang, M., and Zhao, J. (2017). Genetic and phenotypic characteristics of four Chinese families with fundus albipunctatus. Sci. Rep., 7.","DOI":"10.1038\/srep46285"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1167\/iovs.61.3.53","article-title":"RDH5-Related Fundus Albipunctatus in a Large Japanese Cohort","volume":"61","author":"Katagiri","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.ajo.2013.10.021","article-title":"Cone abnormalities in fundus albipunctatus associated with RDH5 mutations assessed using adaptive optics scanning laser ophthalmoscopy","volume":"157","author":"Makiyama","year":"2014","journal-title":"Am. J. Ophthalmol."},{"key":"ref_82","first-page":"1712","article-title":"Fundus albipunctatus: Novel mutations and phenotypic description of Israeli patients","volume":"18","author":"Pras","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1136\/jmedgenet-2016-103837","article-title":"Molecular findings from 537 individuals with inherited retinal disease","volume":"53","author":"Ellingford","year":"2016","journal-title":"J. Med. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Dockery, A., Stephenson, K., Keegan, D., Wynne, N., Silvestri, G., Humphries, P., Kenna, P.F., Carrigan, M., and Farrar, G.J. (2017). Target 5000: Target Capture Sequencing for Inherited Retinal Degenerations. Genes, 8.","DOI":"10.3390\/genes8110304"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Al-Khuzaei, S., Broadgate, S., Foster, C.R., Shah, M., Yu, J., Downes, S.M., and Halford, S. (2021). An Overview of the Genetics of ABCA4 Retinopathies, an Evolving Story. Genes, 12.","DOI":"10.3390\/genes12081241"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Garc\u00eda Boh\u00f3rquez, B., Aller, E., Rodr\u00edguez Mu\u00f1oz, A., Jaijo, T., Garc\u00eda Garc\u00eda, G., and Mill\u00e1n, J.M. (2021). Updating the Genetic Landscape of Inherited Retinal Dystrophies. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.645600"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e2339571","DOI":"10.1001\/jamanetworkopen.2023.39571","article-title":"Rates and Classification of Variants of Uncertain Significance in Hereditary Disease Genetic Testing","volume":"6","author":"Chen","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1001\/jamacardio.2017.5333","article-title":"Association of Racial\/Ethnic Categories With the Ability of Genetic Tests to Detect a Cause of Cardiomyopathy","volume":"3","author":"Landry","year":"2018","journal-title":"JAMA Cardiol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Bea-Mascato, B., Solarat, C., Perea-Romero, I., Jaijo, T., Blanco-Kelly, F., Mill\u00e1n, J.M., Ayuso, C., and Valverde, D. (2021). Prevalent ALMS1 Pathogenic Variants in Spanish Alstr\u00f6m Patients. Genes, 12.","DOI":"10.3390\/genes12020282"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"225","DOI":"10.2174\/138920211795677912","article-title":"Alstr\u00f6m syndrome: Genetics and clinical overview","volume":"12","author":"Marshall","year":"2011","journal-title":"Curr. Genom."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1167\/iovs.11-8026","article-title":"GNAT1 associated with autosomal recessive congenital stationary night blindness","volume":"53","author":"Naeem","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Zeitz, C., M\u00e9j\u00e9case, C., St\u00e9venard, M., Michiels, C., Audo, I., and Marmor, M.F. (2018). A Novel Heterozygous Missense Mutation in GNAT1 Leads to Autosomal Dominant Riggs Type of Congenital Stationary Night Blindness. Biomed. Res. Int., 2018.","DOI":"10.1155\/2018\/7694801"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Kim, H.M., Joo, K., Han, J., and Woo, S.J. (2021). Clinical and Genetic Characteristics of Korean Congenital Stationary Night Blindness Patients. Genes, 12.","DOI":"10.3390\/genes12060789"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1136\/bjophthalmol-2015-306939","article-title":"A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration","volume":"100","author":"Carrigan","year":"2016","journal-title":"Br. J. Ophthalmol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Zenteno, J.C., Garc\u00eda-Monta\u00f1o, L.A., Cruz-Aguilar, M., Ronquillo, J., Rodas-Serrano, A., Aguilar-Castul, L., Matsui, R., Vencedor-Meraz, C.I., Arce-Gonz\u00e1lez, R., and Graue-Wiechers, F. (2020). Extensive genic and allelic heterogeneity underlying inherited retinal dystrophies in Mexican patients molecularly analyzed by next-generation sequencing. Mol. Genet. Genom. Med., 8.","DOI":"10.1002\/mgg3.1044"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"13913","DOI":"10.1073\/pnas.250478897","article-title":"Phototransduction in transgenic mice after targeted deletion of the rod transducin \u03b1-subunit","volume":"97","author":"Calvert","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1080\/13816810.2019.1686159","article-title":"Novel homozygous in-frame deletion of GNAT1 gene causes golden appearance of fundus and reduced scotopic ERGs similar to that in Oguchi disease in Japanese family","volume":"40","author":"Kubota","year":"2019","journal-title":"Ophthalmic Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1038\/s41436-018-0345-5","article-title":"Biallelic sequence and structural variants in RAX2 are a novel cause for autosomal recessive inherited retinal disease","volume":"21","author":"Smith","year":"2019","journal-title":"Genet. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1242\/jcs.112.4.549","article-title":"Intracellular localization and membrane topology of 11-cis retinol dehydrogenase in the retinal pigment epithelium suggest a compartmentalized synthesis of 11-cis retinaldehyde","volume":"112","author":"Simon","year":"1999","journal-title":"J. Cell Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5089","DOI":"10.1167\/iovs.09-3797","article-title":"The 11-cis-retinol dehydrogenase activity of RDH10 and its interaction with visual cycle proteins","volume":"50","author":"Farjo","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4275","DOI":"10.1128\/MCB.20.12.4275-4287.2000","article-title":"Disruption of the 11-cis-retinol dehydrogenase gene leads to accumulation of cis-retinols and cis-retinyl esters","volume":"20","author":"Driessen","year":"2000","journal-title":"Mol. Cell Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/9707","article-title":"Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus","volume":"22","author":"Yamamoto","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_103","first-page":"1558","article-title":"Novel mutations in RDH5 cause fundus albipunctatus in two consanguineous Pakistani families","volume":"18","author":"Ajmal","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1093\/hmg\/ddab316","article-title":"A large animal model of RDH5-associated retinopathy recapitulates important features of the human phenotype","volume":"31","author":"Occelli","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1016\/S0002-9440(10)64453-7","article-title":"Gene transfer of human hepatocyte growth factor into rat skin wounds mediated by liposomes coated with the sendai virus (hemagglutinating virus of Japan)","volume":"161","author":"Nakanishi","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Eisenberger, T., Neuhaus, C., Khan, A.O., Decker, C., Preising, M.N., Friedburg, C., Bieg, A., Gliem, M., Charbel Issa, P., and Holz, F.G. (2013). Increasing the yield in targeted next-generation sequencing by implicating CNV analysis, non-coding exons and the overall variant load: The example of retinal dystrophies. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078496"},{"key":"ref_107","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."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/1\/32\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:55:03Z","timestamp":1760115303000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/1\/32"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,28]]},"references-count":107,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["genes16010032"],"URL":"https:\/\/doi.org\/10.3390\/genes16010032","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,28]]}}}