{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:14:04Z","timestamp":1790475244368,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"International Research Support Initiative Program (IRSIP) of the Higher Education Commission (HEC)","award":["EJP RD COFUND-EJP N\u00b0 825575"],"award-info":[{"award-number":["EJP RD COFUND-EJP N\u00b0 825575"]}]},{"name":"International Research Support Initiative Program (IRSIP) of the Higher Education Commission (HEC)","award":["CD-GE-0621-0809-RAD"],"award-info":[{"award-number":["CD-GE-0621-0809-RAD"]}]},{"name":"International Research Support Initiative Program (IRSIP) of the Higher Education Commission (HEC)","award":["NRPU # 420"],"award-info":[{"award-number":["NRPU # 420"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme","award":["EJP RD COFUND-EJP N\u00b0 825575"],"award-info":[{"award-number":["EJP RD COFUND-EJP N\u00b0 825575"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme","award":["CD-GE-0621-0809-RAD"],"award-info":[{"award-number":["CD-GE-0621-0809-RAD"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme","award":["NRPU # 420"],"award-info":[{"award-number":["NRPU # 420"]}]},{"name":"Foundation Fighting Blindness (FFB)","award":["EJP RD COFUND-EJP N\u00b0 825575"],"award-info":[{"award-number":["EJP RD COFUND-EJP N\u00b0 825575"]}]},{"name":"Foundation Fighting Blindness (FFB)","award":["CD-GE-0621-0809-RAD"],"award-info":[{"award-number":["CD-GE-0621-0809-RAD"]}]},{"name":"Foundation Fighting Blindness (FFB)","award":["NRPU # 420"],"award-info":[{"award-number":["NRPU # 420"]}]},{"name":"National Research Program for University","award":["EJP RD COFUND-EJP N\u00b0 825575"],"award-info":[{"award-number":["EJP RD COFUND-EJP N\u00b0 825575"]}]},{"name":"National Research Program for University","award":["CD-GE-0621-0809-RAD"],"award-info":[{"award-number":["CD-GE-0621-0809-RAD"]}]},{"name":"National Research Program for University","award":["NRPU # 420"],"award-info":[{"award-number":["NRPU # 420"]}]},{"name":"Higher Education Commission, Pakistan","award":["EJP RD COFUND-EJP N\u00b0 825575"],"award-info":[{"award-number":["EJP RD COFUND-EJP N\u00b0 825575"]}]},{"name":"Higher Education Commission, Pakistan","award":["CD-GE-0621-0809-RAD"],"award-info":[{"award-number":["CD-GE-0621-0809-RAD"]}]},{"name":"Higher Education Commission, Pakistan","award":["NRPU # 420"],"award-info":[{"award-number":["NRPU # 420"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Anophthalmia and microphthalmia (A\/M) are among the most severe congenital developmental eye disorders. Despite the advancements in genome screening technologies, more than half of A\/M patients do not receive a molecular diagnosis. We included seven consanguineous families affected with A\/M from Pakistani cohort and an unknown molecular basis. Single gene testing of FOXE3 was performed, followed by genome sequencing for unsolved probands in order to establish a genetic diagnosis for these families. All seven families were provided with a genetic diagnosis. The identified variants were all homozygous, classified as (likely) pathogenic and present in an A\/M-associated gene. Targeted FOXE3 sequencing revealed two previously reported pathogenic FOXE3 variants in four families. In the remaining families, genome sequencing revealed a known pathogenic PXDN variant, a novel 13bp deletion in VSX2, and one novel deep intronic splice variant in PXDN. An in vitro splice assay was performed for the PXDN splice variant which revealed a severe splicing defect. Our study confirmed the utility of genome sequencing as a diagnostic tool for A\/M-affected individuals. Furthermore, the identification of a novel deep intronic pathogenic variant in PXDN highlights the role of non-coding variants in A\/M-disorders and the value of genome sequencing for the identification of this type of variants.<\/jats:p>","DOI":"10.3390\/genes14081573","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T09:14:40Z","timestamp":1690881280000},"page":"1573","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Combined Single Gene Testing and Genome Sequencing as an Effective Diagnostic Approach for Anophthalmia and Microphthalmia Patients"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0316-5131","authenticated-orcid":false,"given":"Rabia","family":"Basharat","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan"},{"name":"Department of Human Genetics, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0389-1518","authenticated-orcid":false,"given":"Kim","family":"Rodenburg","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6464-9245","authenticated-orcid":false,"given":"Mar\u00eda","family":"Rodr\u00edguez-Hidalgo","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"},{"name":"Department of Neuroscience, Biodonostia Health Research Institute, 20014 Donostia-San Sebasti\u00e1n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afeefa","family":"Jarral","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Mirpur University of Science and Technology (MUST), Mirpur 10250, AJK, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0107-6608","authenticated-orcid":false,"given":"Ehsan","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan"},{"name":"Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Corominas","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1693-9699","authenticated-orcid":false,"given":"Christian","family":"Gilissen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syeda Tatheer","family":"Zehra","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usman","family":"Hameed","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Ansar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2912-9265","authenticated-orcid":false,"given":"Suzanne E.","family":"de Bruijn","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,1]]},"reference":[{"key":"ref_1","unstructured":"Mann, I. 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