{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:02:21Z","timestamp":1785402141359,"version":"3.56.0"},"reference-count":102,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY022356, EY018571, EY002520, P30EY010572, EY09076, EY030499"],"award-info":[{"award-number":["EY022356, EY018571, EY002520, P30EY010572, EY09076, EY030499"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"award":["EY022356, EY018571, EY002520, P30EY010572, EY09076, EY030499"],"award-info":[{"award-number":["EY022356, EY018571, EY002520, P30EY010572, EY09076, EY030499"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Non-syndromic retinitis pigmentosa (RP) is characterized by rod\u2013cone degeneration, resulting in night blindness, visual field constriction, and eventual blindness. Recessively inherited RP is predominantly exacerbated in consanguineous populations, such as Pakistan. This study aimed to perform the genetic analysis of sixteen non-syndromic RP segregating Pakistani families, and to summarize the mutation spectrum of non-syndromic RP in our population by reviewing related literature. Methods: We screened 16 non-syndromic RP families using targeted capture panel sequencing of 344 genes related to inherited retinal dystrophies. Variants were prioritized based on rarity (minor allele frequency (MAF) &lt; 0.001 in the gnomAD South Asian subset), pathogenicity assessments using ACMG\/AMP criteria, and REVEL scores (&gt;0.5). Candidate variants were validated for familial segregation through Sanger sequencing. Results: We identified 15 distinct variants across 14 genes associated with non-syndromic retinitis pigmentosa, comprising 6 missense, 7 nonsense, 1 frameshift, and 2 splice-site variants, including 4 novel variants, i.e., p.(Val220Met) and p.(Pro1282SerfsTer2) in RP1, 1 each in PDE6B (c.2021+5G&gt;A), and PRCD p.(Ser38Ter). Homozygosity predominated, underscoring the impact of consanguinity on the burden of autosomal recessive disease in the present cohort, while the CERKL disease-causing mutation, i.e., p.(Arg257Ter), recurred in two families. Conclusions: This study expands Pakistan\u2019s non-syndromic RP mutational spectrum by identifying novel variants in RP1, PDE6B, and PRCD, alongside recurrent CERKL and RHO mutations of the local population. The literature review suggests that RP1, TULP1, and PDE6B are among the most mutated genes in our population, supporting the value of population-specific genetic panels to enhance diagnostics and carrier screening.<\/jats:p>","DOI":"10.3390\/genes17050529","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T15:01:18Z","timestamp":1777474878000},"page":"529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expanding the Mutation Spectrum of Non-Syndromic Retinitis Pigmentosa in Consanguineous Pakistani Families: Unraveling Novel Pathogenic Variants in RP1, PDE6B, and PRCD Genes for Precision Diagnosis"],"prefix":"10.3390","volume":"17","author":[{"given":"Tayyaba","family":"Shan","sequence":"first","affiliation":[{"name":"Department of Zoology, Faculty of Biological Sciences, Quaid-i-Azam University, University Road, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimra","family":"Mukhtar","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Biological Sciences, Quaid-i-Azam University, University Road, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4853-2630","authenticated-orcid":false,"given":"Sayyed Hammad","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Biological Sciences, Quaid-i-Azam University, University Road, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asad","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Biological Sciences, Quaid-i-Azam University, University Road, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asfandyar Ahmad","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Biological Sciences, Quaid-i-Azam University, University Road, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Center for Translational Vision Research, Irvine School of Medicine, University of California, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2742-3559","authenticated-orcid":false,"given":"Meng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Center for Translational Vision Research, Irvine School of Medicine, University of California, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3423-7730","authenticated-orcid":false,"given":"Raeesa","family":"Tehreem","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Biological Sciences, Quaid-i-Azam University, University Road, Islamabad 45320, Pakistan"},{"name":"Department of Biological Sciences, Rawalpindi Medical University, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amtul","family":"Aziz","sequence":"additional","affiliation":[{"name":"Diagnostic Center, Al-Shifa Trust Eye Hospital, Jhelum Road, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3979-7606","authenticated-orcid":false,"given":"Kiran","family":"Afshan","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Biological Sciences, Quaid-i-Azam University, University Road, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4387-9735","authenticated-orcid":false,"given":"Rui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Center for Translational Vision Research, Irvine School of Medicine, University of California, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4959-7832","authenticated-orcid":false,"given":"Sabika","family":"Firasat","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Biological Sciences, Quaid-i-Azam University, University Road, Islamabad 45320, Pakistan"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Garc\u00eda Boh\u00f3rquez, B., Aller, E., Rodr\u00edguez Mu\u00f1oz, A., Jaijo, T., Garc\u00eda, G.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_2","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.2147\/OPTH.S365486","article-title":"Retinitis Pigmentosa: Burden of Disease and Current Unmet Needs","volume":"16","author":"Cross","year":"2022","journal-title":"Clin. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"238","DOI":"10.2174\/138920211795860107","article-title":"Retinitis pigmentosa: Genes and disease mechanisms","volume":"12","author":"Ferrari","year":"2011","journal-title":"Curr. Genom."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1080\/13816810.2019.1675178","article-title":"Next-generation sequencing and its application in diagnosis of retinitis pigmentosa","volume":"40","author":"Salmaninejad","year":"2019","journal-title":"Ophthalmic Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1136\/jmg-2023-109470","article-title":"Diagnostic genome sequencing improves diagnostic yield: A prospective single-centre study in 1000 patients with inherited eye diseases","volume":"61","author":"Weisschuh","year":"2024","journal-title":"J. Med. Genet."},{"key":"ref_6","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_7","unstructured":"O\u2019Neal, T.B., Tripathy, K., and Luther, E.E. (2025). Retinitis Pigmentosa. StatPearls [Internet], StatPearls Publishing."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41431-019-0548-5","article-title":"Diagnostic yield of panel-based genetic testing in syndromic inherited retinal disease","volume":"28","author":"Jiman","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ajo.2022.12.027","article-title":"The Diagnostic Yield of Next Generation Sequencing in Inherited Retinal Diseases: A Systematic Review and Meta-analysis","volume":"249","author":"Gocuk","year":"2023","journal-title":"Am. J. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5759","DOI":"10.3390\/ijms25115759","article-title":"Coexistence of Retinitis Pigmentosa and Ataxia in Patients with PHARC, PCARP, and Oliver\u2013McFarlane Syndromes","volume":"25","author":"Wawrocka","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Marwan, M., Dawood, M., Ullah, M., Shah, I.U., Khan, N., Hassan, M.T., Karam, M., Rawlins, L.E., Baple, E.L., and Crosby, A.H. (2023). Unravelling the genetic basis of retinal dystrophies in Pakistani consanguineous families. BMC Ophthalmol., 23.","DOI":"10.1186\/s12886-023-02948-8"},{"key":"ref_12","first-page":"1734","article-title":"Retinitis pigmentosa genes implicated in South Asian populations: A systematic review","volume":"67","author":"Zafar","year":"2017","journal-title":"J. Pak. Med. Assoc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2470953","DOI":"10.1080\/07853890.2025.2470953","article-title":"Exome sequencing identifies a homozygous splice site variant in RP1 as the underlying cause of autosomal recessive retinitis pigmentosa in a Pakistani family","volume":"57","author":"Rashid","year":"2025","journal-title":"Ann. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41525-025-00488-2","article-title":"A comprehensive genetic landscape of inherited retinal diseases in a large Pakistani cohort","volume":"10","author":"Ullah","year":"2025","journal-title":"npj Genom. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tehreem, R., Chen, I., Shah, M.R., Li, Y., Khan, M.A., Afshan, K., Chen, R., and Firasat, S. (2022). Exome sequencing identified molecular determinants of retinal dystrophies in nine consanguineous Pakistani families. Genes, 13.","DOI":"10.3390\/genes13091630"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Pei, X.M., Yeung, M.H.Y., Wong, A.N.N., Tsang, H.F., Yu, A.C.S., Yim, A.K.Y., and Wong, S.C.C. (2023). Targeted sequencing approach and its clinical applications for the molecular diagnosis of human diseases. Cells, 12.","DOI":"10.3390\/cells12030493"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41525-024-00390-3","article-title":"A cost-effective sequencing method for genetic studies combining high-depth whole exome and low-depth whole genome","volume":"9","author":"Eveleigh","year":"2024","journal-title":"npj Genom. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1001\/archophthalmol.2011.290","article-title":"Identification of Novel Mutations in Pakistani Families With Autosomal Recessive Retinitis Pigmentosa","volume":"129","author":"Azam","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1038\/s41431-025-01833-w","article-title":"Determinants of diagnostic yield in a multi-ethnic Asian inherited retinal disease cohort","volume":"33","author":"Lieviant","year":"2025","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wawrocka, A., Socha, M., Walczak-Sztulpa, J., Koczyk, G., Skorczyk-Werner, A., and Krawczy\u0144ski, M.R. (2023). Molecular Re-Diagnosis with Whole-Exome Sequencing Increases the Diagnostic Yield in Patients with Non-Syndromic Retinitis Pigmentosa. Diagnostics, 13.","DOI":"10.3390\/diagnostics13040730"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature10423","article-title":"Deep sequencing reveals 50 novel genes for recessive cognitive disorders","volume":"478","author":"Najmabadi","year":"2011","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1001\/archophthalmol.2011.267","article-title":"Association of pathogenic mutations in TULP1 with retinitis pigmentosa in consanguineous Pakistani families","volume":"129","author":"Iqbal","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"de Bruijn, S.E., Fadaie, Z., Cremers, F.P., Kremer, H., and Roosing, S. (2021). The impact of modern technologies on molecular diagnostic success rates, with a focus on inherited retinal dystrophy and hearing loss. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062943"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109945","DOI":"10.1016\/j.exer.2024.109945","article-title":"Next-generation sequencing to genetically diagnose a diverse range of inherited eye disorders in 15 consanguineous families from Pakistan","volume":"244","author":"Basharat","year":"2024","journal-title":"Exp. Eye Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/cge.12039","article-title":"Homozygosity mapping identifies genetic defects in four consanguineous families with retinal dystrophy from Pakistan","volume":"84","author":"Hussain","year":"2013","journal-title":"Clin. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.ajhg.2009.09.015","article-title":"Missense mutations in a retinal pigment epithelium protein, bestrophin-1, cause retinitis pigmentosa","volume":"85","author":"Davidson","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_27","first-page":"1960","article-title":"A missense mutation in the nuclear localization signal sequence of CERKL (p. R106S) causes autosomal recessive retinal degeneration","volume":"14","author":"Ali","year":"2008","journal-title":"Mol. Vis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5943","DOI":"10.1167\/iovs.10-5797","article-title":"Homozygosity mapping in patients with cone\u2013rod dystrophy: Novel mutations and clinical characterizations","volume":"51","author":"Littink","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1167\/iovs.07-0865","article-title":"CERKL mutations and associated phenotypes in seven Spanish families with autosomal recessive retinitis pigmentosa","volume":"49","author":"Vallespin","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.ophtha.2010.10.047","article-title":"CLRN1 mutations cause nonsyndromic retinitis pigmentosa","volume":"118","author":"Khan","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_31","first-page":"9","article-title":"Autosomal recessive retinitis pigmentosa in a Pakistani family mapped to CNGA1 with identification of a novel mutation","volume":"10","author":"Zhang","year":"2004","journal-title":"Mol. Vis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"176","DOI":"10.3390\/genes5010176","article-title":"The molecular basis of retinal dystrophies in Pakistan","volume":"5","author":"Khan","year":"2014","journal-title":"Genes"},{"key":"ref_33","unstructured":"D\u2019Atri, I. (2020). Defining the Genetic and Molecular Basis of Inherited Eye Diseases Present in Pakistan. [Ph.D. Thesis, University of Exeter]."},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/S0014-4835(02)00304-4","article-title":"Mutation screening of Pakistani families with congenital eye disorders","volume":"76","author":"Khaliq","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1076\/opge.22.3.163.2222","article-title":"CRB1 mutations may result in retinitis pigmentosa without para-arteriolar RPE preservation","volume":"22","author":"Lotery","year":"2001","journal-title":"Ophthalmic Genet."},{"key":"ref_37","first-page":"2753","article-title":"Missense mutations at homologous positions in the fourth and fifth laminin A G-like domains of eyes shut homolog cause autosomal recessive retinitis pigmentosa","volume":"16","author":"Khan","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1167\/iovs.17-21424","article-title":"Homozygosity mapping and genetic analysis of autosomal recessive retinal dystrophies in 144 consanguineous Pakistani families","volume":"58","author":"Li","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.ajhg.2010.07.004","article-title":"Mutations in IMPG2, encoding interphotoreceptor matrix proteoglycan 2, cause autosomal-recessive retinitis pigmentosa","volume":"87","author":"Collin","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1136\/bjo.2009.171892","article-title":"Nonsense mutation in MERTK causes autosomal recessive retinitis pigmentosa in a consanguineous Pakistani family","volume":"94","author":"Shahzadi","year":"2010","journal-title":"Br. J. Ophthalmol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Rashid, M., Qasim, M., Ishaq, R., Bukhari, S.A., Sajid, Z., Ashfaq, U.A., Haque, A., and Ahmed, Z.M. (2020). Pathogenic variants of AIPL1, MERTK, GUCY2D, and FOXE3 in Pakistani families with clinically heterogeneous eye diseases. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0239748"},{"key":"ref_42","first-page":"816","article-title":"P. arg102ser is a common Pde6\u03b1 mutation causing autosomal recessive retinitis pigmentosa in Pakistani families","volume":"71","author":"Khan","year":"2021","journal-title":"J. Pak. Med. Assoc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9965","DOI":"10.1038\/srep09965","article-title":"Homozygosity mapping reveals novel and known mutations in Pakistani families with inherited retinal dystrophies","volume":"5","author":"Saqib","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"16036","DOI":"10.1038\/hgv.2016.36","article-title":"Mutations in phosphodiesterase 6 identified in familial cases of retinitis pigmentosa","volume":"3","author":"Ullah","year":"2016","journal-title":"Hum. Genome Var."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1167\/iovs.04-1280","article-title":"Autosomal recessive retinitis pigmentosa is associated with mutations in RP1 in three consanguineous Pakistani families","volume":"46","author":"Riazuddin","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_46","first-page":"1283","article-title":"Mutations in the gene encoding the alpha-subunit of rod phosphodiesterase in consanguineous Pakistani families","volume":"12","author":"Riazuddin","year":"2006","journal-title":"Mol. Vis."},{"key":"ref_47","first-page":"1373","article-title":"Mutations in the \u03b2-subunit of rod phosphodiesterase identified in consanguineous Pakistani families with autosomal recessive retinitis pigmentosa","volume":"17","author":"Ali","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ur Rehman, A., Peter, V.G., Quinodoz, M., Rashid, A., Khan, S.A., Superti-Furga, A., and Rivolta, C. (2019). Exploring the genetic landscape of retinal diseases in North-Western Pakistan reveals a high degree of autozygosity and a prevalent founder mutation in ABCA4. Genes, 11.","DOI":"10.3390\/genes11010012"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Aziz, N., Ullah, M., Rashid, A., Hussain, Z., Shah, K., Awan, A., Khan, M., Ullah, I., and Rehman, A.U. (2023). A novel homozygous missense substitution p. Thr313Ile in the PDE6B gene underlies autosomal recessive retinitis pigmentosa in a consanguineous Pakistani family. BMC Ophthalmol., 23.","DOI":"10.1186\/s12886-023-02845-0"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1159\/000530800","article-title":"A novel intronic deletion in PDE6B causes autosomal recessive retinitis pigmentosa by interfering with RNA splicing","volume":"66","author":"Ullah","year":"2023","journal-title":"Ophthalmic Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s00439-007-0395-2","article-title":"Severe retinitis pigmentosa mapped to 4p15 and associated with a novel mutation in the PROM1 gene","volume":"122","author":"Zhang","year":"2007","journal-title":"Hum. Genet."},{"key":"ref_52","first-page":"2526","article-title":"A homozygous p. Glu150Lys mutation in the opsin gene of two Pakistani families with autosomal recessive retinitis pigmentosa","volume":"15","author":"Azam","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1002\/(SICI)1098-1004(1999)13:1<83::AID-HUMU12>3.0.CO;2-5","article-title":"Severe autosomal dominant retinitis pigmentosa caused by a novel rhodopsin mutation (Ter349Glu)","volume":"13","author":"Bessant","year":"1999","journal-title":"Hum. Mutat."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1136\/jmg.2004.024281","article-title":"Novel association of RP1 gene mutations with autosomal recessive retinitis pigmentosa","volume":"42","author":"Khaliq","year":"2005","journal-title":"J. Med. Genet."},{"key":"ref_55","first-page":"610","article-title":"Loss of function mutations in RP1 are responsible for retinitis pigmentosa in consanguineous familial cases","volume":"22","author":"Kabir","year":"2016","journal-title":"Mol. Vis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/78182","article-title":"Mutational hot spot within a new RPGR exon in X-linked retinitis pigmentosa","volume":"25","author":"Vervoort","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1136\/jmg.2005.035055","article-title":"Identification of novel mutations in the SEMA4A gene associated with retinal degenerative diseases","volume":"43","author":"Abid","year":"2006","journal-title":"J. Med. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.ajhg.2010.04.001","article-title":"A splice-site mutation in a retina-specific exon of BBS8 causes nonsyndromic retinitis pigmentosa","volume":"86","author":"Riazuddin","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_59","first-page":"1226","article-title":"Identification of recurrent and novel mutations in TULP1 in Pakistani families with early-onset retinitis pigmentosa","volume":"18","author":"Ajmal","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Maria, M., Ajmal, M., Azam, M., Waheed, N.K., Siddiqui, S.N., Mustafa, B., Ayub, H., Ali, L., Ahmad, S., and Micheal, S. (2015). Homozygosity mapping and targeted sanger sequencing reveal genetic defects underlying inherited retinal disease in families from pakistan. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119806"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Khan, A., Bai, X., Umair, M., Han, S., Habulieti, X., Wang, R., and Zhang, X. (2020). Novel homozygous TULP1 and RPE65 variants underlies recessive Retinitis pigmentosa. Preprint.","DOI":"10.20944\/preprints202009.0062.v1"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.ajhg.2010.08.003","article-title":"A mutation in ZNF513, a putative regulator of photoreceptor development, causes autosomal-recessive retinitis pigmentosa","volume":"87","author":"Li","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.ajo.2009.12.034","article-title":"A novel locus for autosomal recessive retinitis pigmentosa in a consanguineous Pakistani family maps to chromosome 2p","volume":"149","author":"Naz","year":"2010","journal-title":"Am. J. Ophthalmol."},{"key":"ref_64","first-page":"236","article-title":"Novel C8orf37 mutations cause retinitis pigmentosa in consanguineous families of Pakistani origin","volume":"21","author":"Ravesh","year":"2015","journal-title":"Mol. Vis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1038\/eye.2015.93","article-title":"Diverse clinical phenotypes associated with a nonsense mutation in FAM161A","volume":"29","author":"Rose","year":"2015","journal-title":"Eye"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.ophtha.2014.07.057","article-title":"Phenotypic variability associated with the D226N allele of IMPDH1","volume":"122","author":"Ali","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/s13258-015-0311-4","article-title":"Whole-exome sequencing identifies a novel LRAT mutation underlying retinitis punctata albescens in a consanguineous Pakistani family","volume":"37","author":"Jelani","year":"2015","journal-title":"Genes Genom."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s40246-018-0165-3","article-title":"A novel LRAT mutation affecting splicing in a family with early onset retinitis pigmentosa","volume":"12","author":"Chen","year":"2018","journal-title":"Hum. Genom."},{"key":"ref_69","first-page":"1554","article-title":"Novel mutations in RPE65 identified in consanguineous Pakistani families with retinal dystrophy","volume":"19","author":"Kabir","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1167\/iovs.15-17976","article-title":"Nonsyndromic retinal dystrophy due to bi-allelic mutations in the ciliary transport gene IFT140","volume":"57","author":"Hull","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Li, L., Jiao, X., D\u2019Atri, I., Ono, F., Nelson, R., Chan, C.-C., Nakaya, N., Ma, Z., Ma, Y., and Cai, X. (2018). Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007504"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4552","DOI":"10.1167\/iovs.18-23849","article-title":"Confirmation of the role of DHX38 in the etiology of early-onset retinitis pigmentosa","volume":"59","author":"Latif","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s13258-018-0657-5","article-title":"A novel mutation in RDH5 gene causes retinitis pigmentosa in consanguineous Pakistani family","volume":"40","author":"Sultan","year":"2018","journal-title":"Genes Genom."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Astuti, G.D., van Den Born, L.I., Khan, M.I., Hamel, C.P., Bocquet, B., Manes, G., Quinodoz, M., Ali, M., Toomes, C., and McKibbin, M. (2018). Identification of inherited retinal disease-associated genetic variants in 11 candidate genes. Genes, 9.","DOI":"10.3390\/genes9010021"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1159\/000545606","article-title":"Autosomal Dominant RP1 c.2613dupA (p.Arg872Thrfs*2) Variant Retinitis Pigmentosa Shows Linear Loss of the Ellipsoid Zone over Time with Highly Variable Phenotype","volume":"248","author":"Foa","year":"2025","journal-title":"Ophthalmologica"},{"key":"ref_76","first-page":"2411","article-title":"Identification of a novel nonsense mutation in RP1 that causes autosomal recessive retinitis pigmentosa in an Indonesian family","volume":"18","author":"Siemiatkowska","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2721","DOI":"10.1016\/j.ajpath.2014.06.010","article-title":"A murine RP1 missense mutation causes protein mislocalization and slowly progressive photoreceptor degeneration","volume":"184","author":"Song","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1136\/bjophthalmol-2018-313672","article-title":"Expanding the retinal phenotype of RP1: From retinitis pigmentosa to a novel and singular macular dystrophy","volume":"104","author":"Riera","year":"2020","journal-title":"Br. J. Ophthalmol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1038\/s41598-020-58243-9","article-title":"Retinitis Pigmentosa Due to Rp1 Biallelic Variants","volume":"10","author":"Silva","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_80","first-page":"1830","article-title":"Retinitis Pigmentosa due to RP1 variants, phenotype and genotype aspects","volume":"59","author":"Salles","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Kuehlewein, L., Zobor, D., Stingl, K., Kempf, M., Nasser, F., Bernd, A., Biskup, S., Cremers, F.P., Khan, M.I., and Mazzola, P. (2021). Clinical phenotype of PDE6B-associated retinitis pigmentosa. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052374"},{"key":"ref_82","first-page":"155","article-title":"A novel intronic mutation of PDE6B is a major cause of autosomal recessive retinitis pigmentosa among Caucasus Jews","volume":"25","author":"Tatour","year":"2019","journal-title":"Mol. Vis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"13087","DOI":"10.1073\/pnas.1906421116","article-title":"PRCD is essential for high-fidelity photoreceptor disc formation","volume":"116","author":"Spencer","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.ygeno.2006.07.007","article-title":"Identical mutation in a novel retinal gene causes progressive rod\u2013cone degeneration in dogs and retinitis pigmentosa in humans","volume":"88","author":"Zangerl","year":"2006","journal-title":"Genomics"},{"key":"ref_85","first-page":"1350","article-title":"Identification of a novel mutation in the PRCD gene causing autosomal recessive retinitis pigmentosa in a Turkish family","volume":"19","author":"Pach","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1136\/jmg.2009.073619","article-title":"Identification of a prevalent founder mutation in an Israeli Muslim Arab village confirms the role of PRCD in the aetiology of retinitis pigmentosa in humans","volume":"47","author":"Nevet","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1159\/000445690","article-title":"A Cost-Effective Mutation Screening Strategy for Inherited Retinal Dystrophies","volume":"56","author":"Barandika","year":"2016","journal-title":"Ophthalmic Res."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Azab, B., Dardas, Z., Aburizeg, D., Al-Bdour, M., Abu-Ameerh, M., Saleh, T., Barham, R., Maswadi, R., Ababneh, N.A., and Alsalem, M. (2021). Unique Variant Spectrum in a Jordanian Cohort with Inherited Retinal Dystrophies. Genes, 12.","DOI":"10.3390\/genes12040593"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Tawfik, C.A., Elbagoury, N.M., Khater, N.I., and Essawi, M.L. (2022). Mutation analysis reveals novel and known mutations in SAG gene in first two Egyptian families with Oguchi disease. BMC Ophthalmol., 22.","DOI":"10.1186\/s12886-022-02444-5"},{"key":"ref_90","first-page":"3118","article-title":"S Antigen (SAG) Mutations are an important cause of retinitis pigmentosa in Texas patients of Hispanic descent","volume":"65","author":"Espinoza","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2774","DOI":"10.1167\/iovs.16-21341","article-title":"A Novel Dominant Mutation in SAG, the Arrestin-1 Gene, Is a Common Cause of Retinitis Pigmentosa in Hispanic Families in the Southwestern United States","volume":"58","author":"Sullivan","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.4103\/IJO.IJO_2579_22","article-title":"Next-generation sequencing-based genetic testing and phenotype correlation in retinitis pigmentosa patients from India","volume":"71","author":"Sen","year":"2023","journal-title":"Indian J. Ophthalmol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e181","DOI":"10.1111\/aos.14181","article-title":"RPE 65 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_94","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1007\/s00417-017-3679-9","article-title":"A novel MERTK mutation causing retinitis pigmentosa","volume":"255","author":"Shah","year":"2017","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1167\/iovs.16-20864","article-title":"Novel 25 kb Deletion of MERTK Causes Retinitis Pigmentosa with Severe Progression","volume":"58","author":"Evans","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1007\/s00438-022-01917-y","article-title":"Whole-exome sequencing deciphers the genetic profile of visual impairments in patients from Southwest Iran","volume":"297","author":"Zamani","year":"2022","journal-title":"Mol. Genet. Genom."},{"key":"ref_97","first-page":"2550","article-title":"Mutation analysis of 272 Spanish families affected by autosomal recessive retinitis pigmentosa using a genotyping microarray","volume":"16","author":"Cantalapiedra","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.18240\/ijo.2021.12.06","article-title":"Novel mutations in PDE6A and CDHR1 cause retinitis pigmentosa in Pakistani families","volume":"14","author":"Dawood","year":"2021","journal-title":"Int. J. Ophthalmol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2710","DOI":"10.1073\/pnas.1913179117","article-title":"Worldwide carrier frequency and genetic prevalence of autosomal recessive inherited retinal diseases","volume":"117","author":"Hanany","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.4103\/ijo.IJO_46_22","article-title":"Genetic dissection of non-syndromic retinitis pigmentosa","volume":"70","author":"Bhardwaj","year":"2022","journal-title":"Indian J. Ophthalmol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Xia, C.-H., Liu, H., Li, M., Zhang, H., Xing, X., and Gong, X. (2023). Identification and characterization of retinitis pigmentosa in a novel mouse model caused by PDE6B-T592I. Biomedicines, 11.","DOI":"10.3390\/biomedicines11123173"},{"key":"ref_102","first-page":"165","article-title":"Retinitis Pigmentosa Genes Implicated in the Population of America: A Systematic Review","volume":"42","author":"Torres","year":"2025","journal-title":"Acta Fac. Medicae Naissensis"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/5\/529\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T04:14:19Z","timestamp":1778732059000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/5\/529"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":102,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["genes17050529"],"URL":"https:\/\/doi.org\/10.3390\/genes17050529","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,29]]}}}