{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T12:57:41Z","timestamp":1784897861404,"version":"3.55.0"},"reference-count":65,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Swiss National Science Foundation","award":["320030_212959"],"award-info":[{"award-number":["320030_212959"]}]},{"name":"the Prix Claire et Selma Kattenburg","award":["320030_212959"],"award-info":[{"award-number":["320030_212959"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Degenerative and developmental eye disorders, including inherited retinal dystrophies (IRDs), anophthalmia, and congenital cataracts arise from genetic mutations, causing progressive vision loss or congenital structural abnormalities. IRDs include a group of rare, genetically, and clinically heterogeneous retinal diseases. It is caused by variations in at least 324 genes, affecting numerous retinal regions. In addition to IRDs, other developmental eye disorders such as anophthalmia and congenital cataracts also have a strong genetic basis. Autosomal recessive IRDs, anophthalmia, and congenital cataracts are common in consanguineous populations. In many endogamous populations, including those in Pakistan, a significant proportion of IRD and anophthalmia cases remain genetically undiagnosed. The present study investigated the variations in IRDs, anophthalmia, and congenital cataracts genes in 50 affected families. These unrelated consanguineous families were recruited from the different provinces of Pakistan including Punjab, Khyber Pakhtoon Khwa, Sindh, Gilgit Baltistan, and Azad Kashmir. Whole exome sequencing (WES) was conducted for the proband of each family. An in-house customized pipeline examined the data, and bioinformatics analysis predicted the pathogenic effects of identified variants. The relevant identified DNA variants of selected families were assessed in parents and healthy siblings via Sanger sequencing. WES identified 12 novel variants across 10 known IRD-associated genes. The four most frequently implicated genes were CRB1 (14.3%), GUCY2D (9.5%), AIPL1 (9.5%), and CERKL (7.1%) that together accounted for 40.4% of all molecularly diagnosed cases. Additionally, 25 reported variants in 19 known IRDs, anophthalmia, and congenital cataracts-associated genes were found. Among the identified variants, p. Trp278X, a stop\u2013gain mutation in the AIPL1 (NM_014336) gene, was the most common causative variant detected. The most frequently observed phenotype was retinitis pigmentosa (46.5%) followed by Leber congenital amaurosis (18.6%). Furthermore, 98% of pedigrees (49 out of 50) were affected by autosomal recessive IRDs, anophthalmia and congenital cataracts. The discovery of 12 novel likely pathogenic variants in 10 IRD genes, 25 reported variants in 19 known IRDs, anophthalmia and congenital cataracts genes, atypical phenotypes, and inter and intra-familial variability underscores the genetic and phenotypic heterogeneity of developmental and degenerative eye disorders in the Pakistani population and further expands the mutational spectrum of genes associated with these ocular disorders.<\/jats:p>","DOI":"10.3390\/ijms26062715","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T06:02:40Z","timestamp":1742277760000},"page":"2715","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Deciphering the Genetic Basis of Degenerative and Developmental Eye Disorders in 50 Pakistani Consanguineous Families Using Whole-Exome Sequencing"],"prefix":"10.3390","volume":"26","author":[{"given":"Ainee","family":"Zafar","sequence":"first","affiliation":[{"name":"Department of Zoology, Wildlife and Fisheries, PMAS-Arid Agriculture University Rawalpindi, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5605-7191","authenticated-orcid":false,"given":"Ruqia Mehmood","family":"Baig","sequence":"additional","affiliation":[{"name":"Department of Zoology, Wildlife and Fisheries, PMAS-Arid Agriculture University Rawalpindi, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abida","family":"Arshad","sequence":"additional","affiliation":[{"name":"Department of Zoology, Wildlife and Fisheries, PMAS-Arid Agriculture University Rawalpindi, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdur","family":"Rashid","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Lausanne, Jules Gonin Eye Hospital, Fondation Asile Des Aveugles, 1004 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Oreshkov","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Lausanne, Jules Gonin Eye Hospital, Fondation Asile Des Aveugles, 1004 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8686-4461","authenticated-orcid":false,"given":"Helen Nabiryo","family":"Frederiksen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Lausanne, Jules Gonin Eye Hospital, Fondation Asile Des Aveugles, 1004 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Ansar","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Lausanne, Jules Gonin Eye Hospital, Fondation Asile Des Aveugles, 1004 Lausanne, Switzerland"},{"name":"Advanced Molecular Genetics and Genomics Disease Research and Treatment Centre, Dow University of Health Sciences, Karachi 74200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e575","DOI":"10.1016\/j.jcjo.2023.08.006","article-title":"Molecular genetic diagnostics for inherited retinal dystrophies in the clinical setting","volume":"59","author":"Kolawole","year":"2024","journal-title":"Can. J. Ophthalmol."},{"key":"ref_2","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_3","first-page":"4481-F0268","article-title":"Current management of Inherited Retinal Degenerations (IRD) patients in Europe. Results of a 2 years follow-up multinational survey by EVICR. net and ERN-EYE","volume":"63","author":"Tavares","year":"2022","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1001\/jama.2023.26074","article-title":"Age-related macular degeneration: A review","volume":"331","author":"Fleckenstein","year":"2024","journal-title":"Jama"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1056\/NEJMoa1306555","article-title":"Clinical whole-exome sequencing for the diagnosis of mendelian disorders","volume":"369","author":"Yang","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Rashid, M., Qasim, M., Ishaq, R., Bukhari, S., Sajid, Z., Ashfaq, U., Haque, A., and Ahmed, Z. (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_7","doi-asserted-by":"crossref","unstructured":"Tehreem, R., Chen, I., Shah, M., Li, Y., Khan, M., 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_8","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.exer.2005.11.010","article-title":"Molecular basis of human Usher syndrome: Deciphering the meshes of the Usher protein network provides insights into the pathomechanisms of the Usher disease","volume":"83","author":"Reiners","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"224","DOI":"10.4103\/kjo.kjo_34_24","article-title":"A brief review on microphthalmia and anophthalmia","volume":"36","author":"Periyandavan","year":"2024","journal-title":"Kerala J. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"107","DOI":"10.4274\/tjo.galenos.2020.08377","article-title":"Congenital cataract and its genetics: The era of next-generation sequencing","volume":"51","author":"Utine","year":"2021","journal-title":"Turk. J. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s12687-018-0401-5","article-title":"Consanguinity and its association with visual impairment in southern India: The Pavagada Pediatric Eye Disease Study 2","volume":"10","author":"Kemmanu","year":"2019","journal-title":"J. Community Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s12687-011-0072-y","article-title":"Consanguineous marriages: Preconception consultation in primary health care settings","volume":"3","author":"Hamamy","year":"2012","journal-title":"J. Community Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1002\/ajmg.a.62856","article-title":"Whole exome sequencing identifies a novel compound heterozygous GFM1 variant underlying developmental delay, dystonia, polymicrogyria, and severe intellectual disability in a Pakhtun family","volume":"188","author":"Khan","year":"2022","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1006\/jmbi.2000.3996","article-title":"Endostatins derived from collagens XV and XVIII differ in structural and binding properties, tissue distribution and anti-angiogenic activity","volume":"301","author":"Sasaki","year":"2000","journal-title":"J. Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S0272-6386(97)90006-8","article-title":"A vertical (pseudodominant) pattern of inheritance in the autosomal recessive disease primary hyperoxaluria type 1: Lack of relationship between genotype, enzymic phenotype, and disease severity","volume":"29","author":"Hoppe","year":"1997","journal-title":"Am. J. Kidney Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s12687-015-0252-2","article-title":"Addressing key issues in the consanguinity-related risk of autosomal recessive disorders in consanguineous communities: Lessons from a qualitative study of British Pakistanis","volume":"7","author":"Darr","year":"2016","journal-title":"J. Community Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1016\/j.ophtha.2020.04.008","article-title":"Genetic basis of inherited retinal disease in a molecularly characterized cohort of more than 3000 families from the United Kingdom","volume":"127","author":"Pontikos","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Munir, A., Afsar, S., and Rehman, A. (2024). A systematic review of inherited retinal dystrophies in Pakistan: Updates from 1999 to April 2023. BMC Ophthalmol., 24.","DOI":"10.1186\/s12886-024-03319-7"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ur Rehman, A., Peter, V., Quinodoz, M., Rashid, A., Khan, S., 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_21","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/S0140-6736(24)02812-5","article-title":"Gene therapy in children with AIPL1-associated severe retinal dystrophy: An open-label, first-in-human interventional study","volume":"405","author":"Michaelides","year":"2025","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5510","DOI":"10.1167\/iovs.14-14359","article-title":"Molecular diagnostic testing by eyeGENE: Analysis of patients with hereditary retinal dystrophy phenotypes involving central vision loss","volume":"55","author":"Alapati","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","first-page":"470","article-title":"Next-generation sequencing to solve complex inherited retinal dystrophy: A case series of multiple genes contributing to disease in extended families","volume":"23","author":"Jones","year":"2017","journal-title":"Mol. Vis."},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.ajhg.2020.09.002","article-title":"Structural variants create new topological-associated domains and ectopic retinal enhancer-gene contact in dominant retinitis pigmentosa","volume":"107","author":"Bruijn","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1136\/jmg.26.4.267","article-title":"Consanguinity related prenatal and postnatal mortality of the populations of seven Pakistani Punjab cities","volume":"26","author":"Shami","year":"1989","journal-title":"J. Med. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"(1998). Hussain The impact of consanguinity and inbreeding on perinatal mortality in Karachi, Pakistan. Paediatr. Perinat. Epidemiol., 12, 370\u2013382.","DOI":"10.1046\/j.1365-3016.1998.00146.x"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Biswas, P., Villanueva, A., Soto-Hermida, A., Duncan, J., Matsui, H., Borooah, S., Kurmanov, B., Richard, G., Khan, S., 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_29","doi-asserted-by":"crossref","unstructured":"Maranhao, B., Biswas, P., Gottsch, A., Navani, M., Naeem, M., Suk, J., Chu, J., Khan, S., Poleman, R., and Akram, J. (2015). Investigating the molecular basis of retinal degeneration in a familial cohort of Pakistani decent by exome sequencing. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136561"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1097\/APO.0000000000000227","article-title":"Retinitis pigmentosa: Progress and perspective","volume":"5","author":"Zhang","year":"2016","journal-title":"Asia-Pac. J. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ajo.2020.10.006","article-title":"Clinical and genetic analysis of 63 families demonstrating early and advanced characteristic fundus as the signature of CRB1 mutations","volume":"223","author":"Wang","year":"2021","journal-title":"Am. J. Ophthalmol."},{"key":"ref_32","first-page":"1","article-title":"AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration","volume":"20","author":"Li","year":"2014","journal-title":"Mol. Vis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.ygeno.2014.02.006","article-title":"exomeSuite: Whole exome sequence variant filtering tool for rapid identification of putative disease causing SNVs\/indels","volume":"103","author":"Maranhao","year":"2014","journal-title":"Genomics"},{"key":"ref_34","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_35","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_36","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1111\/padr.12678","article-title":"Intensive kinship, development, and demography: Why Pakistan has the highest rates of cousin marriage in the world","volume":"50","author":"Shenk","year":"2024","journal-title":"Popul. Dev. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1093\/hmg\/ddy180","article-title":"Visual impairment and progressive phthisis bulbi caused by recessive pathogenic variant in MARK3","volume":"27","author":"Ansar","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows\u2013Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"DePristo","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ng.2892","article-title":"A general framework for estimating the relative pathogenicity of human genetic variants","volume":"46","author":"Kircher","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1101\/gr.3577405","article-title":"Distribution and intensity of constraint in mammalian genomic sequence","volume":"15","author":"Cooper","year":"2005","journal-title":"Genome Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.ajhg.2017.01.004","article-title":"InterVar: Clinical interpretation of genetic variants by the 2015 ACMG-AMP guidelines","volume":"100","author":"Li","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"13534","DOI":"10.1093\/nar\/gku1206","article-title":"In silico prediction of splice-altering single nucleotide variants in the human genome","volume":"42","author":"Jian","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/s10528-017-9828-3","article-title":"Genetic testing of non-familial deaf patients for CIB2 and GJB2 mutations: Phenotype and genetic counseling","volume":"55","author":"Shaikh","year":"2017","journal-title":"Biochem. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/gim.2017.113","article-title":"Biallelic variants in LINGO1 are associated with autosomal recessive intellectual disability, microcephaly, speech and motor delay","volume":"20","author":"Ansar","year":"2018","journal-title":"Genet. Med."},{"key":"ref_47","first-page":"1030","article-title":"MetaDome: Pathogenicity analysis of genetic variants through aggregation of homologous human protein domains","volume":"40","author":"Wiel","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Wang, X., Zein, W., D\u2019Souza, L., Roberson, C., Wetherby, K., He, H., Villarta, A., Turriff, A., Johnson, K., and Fann, Y. (2017). Applying next generation sequencing with microdroplet PCR to determine the disease-causing mutations in retinal dystrophies. BMC Ophthalmol., 17.","DOI":"10.1186\/s12886-017-0549-5"},{"key":"ref_49","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_50","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.gim.2021.09.015","article-title":"The importance of automation in genetic diagnosis: Lessons from analyzing an inherited retinal degeneration cohort with the Mendelian Analysis Toolkit (MATK)","volume":"24","author":"Zampaglione","year":"2022","journal-title":"Genet. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1006\/mgme.2000.3001","article-title":"Prevalence of AIPL1 mutations in inherited retinal degenerative disease","volume":"70","author":"Sohocki","year":"2000","journal-title":"Mol. Genet. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1093\/brain\/awab344","article-title":"Translating genetic and functional data into clinical practice: A series of 223 families with myotonia","volume":"145","author":"Suetterlin","year":"2022","journal-title":"Brain"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"NP6","DOI":"10.1177\/11206721231155042","article-title":"RPGRIP1 variant associated with pigmented paravenous chorioretinal atrophy","volume":"33","author":"Bianco","year":"2023","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"McGuigan, D., Heon, E., Cideciyan, A., Ratnapriya, R., Lu, M., Sumaroka, A., Roman, A., Batmanabane, V., Garafalo, A., and Stone, E. (2017). EYS mutations causing autosomal recessive retinitis pigmentosa: Changes of retinal structure and function with disease progression. Genes, 8.","DOI":"10.3390\/genes8070178"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1167\/iovs.16-19936","article-title":"Mutation spectrum of the ABCA4 gene in 335 Stargardt disease patients from a multicenter German cohort\u2014Impact of selected deep intronic variants and common SNPs","volume":"58","author":"Schulz","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1093\/hmg\/ddab142","article-title":"Comprehensive phenotypic and functional analysis of dominant and recessive FOXE3 alleles in ocular developmental disorders","volume":"30","author":"Reis","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1046\/j.1432-1033.2003.03538.x","article-title":"Functional analysis of disease-causing mutations in human galactokinase","volume":"270","author":"Timson","year":"2003","journal-title":"Eur. J. Biochem."},{"key":"ref_58","first-page":"144","article-title":"Identities and frequencies of variants in CYP1B1 causing primary congenital glaucoma in Pakistan","volume":"25","author":"Rashid","year":"2019","journal-title":"Mol. Vis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s13023-014-0168-7","article-title":"Targeted next generation sequencing for molecular diagnosis of Usher syndrome","volume":"9","author":"Aparisi","year":"2014","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ajo.2019.10.019","article-title":"GUCY2D-associated Leber congenital amaurosis: A retrospective natural history study in preparation for trials of novel therapies","volume":"210","author":"Bouzia","year":"2020","journal-title":"Am. J. Ophthalmol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1002\/ajmg.a.37029","article-title":"Mutations in LONP1, a mitochondrial matrix protease, cause CODAS syndrome","volume":"167","author":"Dikoglu","year":"2015","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1111\/ceo.14166","article-title":"Expanding the phenotypic spectrum of CYP1B1 associated primary congenital glaucoma","volume":"50","author":"Gupta","year":"2022","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1001\/archophthalmol.2010.309","article-title":"Genotype-phenotype correlation for leber congenital amaurosis in Northern Pakistan","volume":"128","author":"McKibbin","year":"2010","journal-title":"Arch. Ophthalmol."},{"key":"ref_64","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_65","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41439-020-00122-w","article-title":"Expanding the genetic spectrum of choroideremia in an Australian cohort: Report of five novel CHM variants","volume":"7","author":"McLaren","year":"2020","journal-title":"Hum. Genome Var."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/6\/2715\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:55:41Z","timestamp":1760028941000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/6\/2715"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,18]]},"references-count":65,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26062715"],"URL":"https:\/\/doi.org\/10.3390\/ijms26062715","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,18]]}}}