{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:17:08Z","timestamp":1792621028488,"version":"4.5.0"},"reference-count":170,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T00:00:00Z","timestamp":1576540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205174\/Z\/16\/Z"],"award-info":[{"award-number":["205174\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The transcription factor PAX6 is essential in ocular development in vertebrates, being considered the master regulator of the eye. During eye development, it is essential for the correct patterning and formation of the multi-layered optic cup and it is involved in the developing lens and corneal epithelium. In adulthood, it is mostly expressed in cornea, iris, and lens. PAX6 is a dosage-sensitive gene and it is highly regulated by several elements located upstream, downstream, and within the gene. There are more than 500 different mutations described to affect PAX6 and its regulatory regions, the majority of which lead to PAX6 haploinsufficiency, causing several ocular and systemic abnormalities. Aniridia is an autosomal dominant disorder that is marked by the complete or partial absence of the iris, foveal hypoplasia, and nystagmus, and is caused by heterozygous PAX6 mutations. Other ocular abnormalities have also been associated with PAX6 changes, and genotype-phenotype correlations are emerging. This review will cover recent advancements in PAX6 regulation, particularly the role of several enhancers that are known to regulate PAX6 during eye development and disease. We will also present an updated overview of the mutation spectrum, where an increasing number of mutations in the non-coding regions have been reported. Novel genotype-phenotype correlations will also be discussed.<\/jats:p>","DOI":"10.3390\/genes10121050","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T03:19:36Z","timestamp":1576811976000},"page":"1050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":179,"title":["The Spectrum of PAX6 Mutations and Genotype-Phenotype Correlations in the Eye"],"prefix":"10.3390","volume":"10","author":[{"given":"Dulce","family":"Lima Cunha","sequence":"first","affiliation":[{"name":"Institute of Ophthalmology, UCL, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Arno","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, UCL, London EC1V 9EL, UK"},{"name":"Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"},{"name":"Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0087-1626","authenticated-orcid":false,"given":"Marta","family":"Corton","sequence":"additional","affiliation":[{"name":"Department of Genetics &amp; Genomics, Instituto de Investigaci\u00f3n Sanitaria-Fundaci\u00f3n Jim\u00e9nez D\u00edaz University Hospital\u2014Universidad Aut\u00f3noma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain"},{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-5360","authenticated-orcid":false,"given":"Mariya","family":"Moosajee","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, UCL, London EC1V 9EL, UK"},{"name":"Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"},{"name":"Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1146\/annurev.neuro.20.1.483","article-title":"PAX-6 in development and evolution","volume":"20","author":"Callaerts","year":"1997","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/0092-8674(91)90284-6","article-title":"Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region","volume":"67","author":"Ton","year":"1991","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/0888-7543(91)90151-4","article-title":"Pax: A murine multigene family of paired box-containing genes","volume":"11","author":"Walther","year":"1991","journal-title":"Genomics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/354522a0","article-title":"Mouse small eye results from mutations in a paired-like homeobox-containing gene","volume":"354","author":"Hill","year":"1991","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/ng0892-328","article-title":"The human PAX6 gene is mutated in two patients with aniridia","volume":"1","author":"Jordan","year":"1992","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/353267a0","article-title":"Expression pattern of zebrafish pax genes suggests a role in early brain regionalization","volume":"353","author":"Krauss","year":"1991","journal-title":"Nature"},{"key":"ref_7","first-page":"1721","article-title":"Characterization of a paired box- and homeobox-containing quail gene (Pax-QNR) expressed in the neuroretina","volume":"7","author":"Martin","year":"1992","journal-title":"Oncogene"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1126\/science.7914031","article-title":"Homology of the eyeless gene of Drosophila to the Small eye gene in mice and Aniridia in humans","volume":"265","author":"Quiring","year":"1994","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1126\/science.7892602","article-title":"Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila","volume":"267","author":"Halder","year":"1995","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4213","DOI":"10.1242\/dev.126.19.4213","article-title":"Pax6 induces ectopic eyes in a vertebrate","volume":"126","author":"Chow","year":"1999","journal-title":"Development"},{"key":"ref_11","first-page":"501","article-title":"Expression pattern of PAX3 and PAX6 genes during human embryogenesis","volume":"43","author":"Terzic","year":"1999","journal-title":"Int. J. Dev. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.preteyeres.2012.04.002","article-title":"Pax6: A multi-level regulator of ocular development","volume":"31","author":"Shaham","year":"2012","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/sj.eye.6702166","article-title":"Continuous expression of the homeobox gene Pax6 in the ageing human retina","volume":"21","author":"Stanescu","year":"2007","journal-title":"Eye"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1038\/ejhg.2016.73","article-title":"Clinical utility gene card for: Aniridia","volume":"24","author":"Richardson","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_15","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Stephens, K., and Amemiya, A. (2018). PAX6-Related Aniridia. GeneReviews((R)), University of Washington."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.neulet.2009.07.021","article-title":"A novel missense mutation (Leu46Val) of PAX6 found in an autistic patient","volume":"462","author":"Maekawa","year":"2009","journal-title":"Neurosci. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.brainres.2018.02.041","article-title":"The role of Pax6 in brain development and its impact on pathogenesis of autism spectrum disorder","volume":"1705","author":"Kikkawa","year":"2019","journal-title":"Brain Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s00439-008-0484-x","article-title":"Pax6 3\u2032 deletion results in aniridia, autism and mental retardation","volume":"123","author":"Davis","year":"2008","journal-title":"Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.ando.2012.10.001","article-title":"Pituitary function and glucose tolerance in a family with a PAX6 mutation","volume":"73","author":"Borot","year":"2012","journal-title":"Ann. D\u2019Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1055\/a-0822-3637","article-title":"Congenital Hypopituitarism: Various Genes, Various Phenotypes","volume":"51","author":"Xatzipsalti","year":"2019","journal-title":"Horm. Metab. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/jsr.12345","article-title":"Pineal hypoplasia, reduced melatonin and sleep disturbance in patients with PAX6 haploinsufficiency","volume":"25","author":"Hanish","year":"2016","journal-title":"J. Sleep Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/ana.10576","article-title":"Polymicrogyria and absence of pineal gland due to PAX6 mutation","volume":"53","author":"Mitchell","year":"2003","journal-title":"Ann. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1080\/02713683.2019.1649704","article-title":"Novel Intragenic PAX6 Deletion in a Pedigree with Aniridia, Morbid Obesity, and Diabetes","volume":"45","author":"Boese","year":"2020","journal-title":"Curr. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"107792","DOI":"10.1016\/j.diabres.2019.107792","article-title":"PAX proteins and their role in pancreas","volume":"155","author":"Panneerselvam","year":"2019","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1093\/hmg\/10.19.2049","article-title":"Aniridia-associated translocations, DNase hypersensitivity, sequence comparison and transgenic analysis redefine the functional domain of PAX6","volume":"10","author":"Kleinjan","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/j.ajhg.2013.10.028","article-title":"Disruption of autoregulatory feedback by a mutation in a remote, ultraconserved PAX6 enhancer causes aniridia","volume":"93","author":"Bhatia","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/ng1192-232","article-title":"Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene","volume":"2","author":"Glaser","year":"1992","journal-title":"Nat. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1093\/nar\/gki562","article-title":"The third helix of the homeodomain of paired class homeodomain proteins acts as a recognition helix both for DNA and protein interactions","volume":"33","author":"Bruun","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1093\/hmg\/10.9.911","article-title":"Missense mutation at the C-terminus of PAX6 negatively modulates homeodomain function","volume":"10","author":"Singh","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7210","DOI":"10.1074\/jbc.273.13.7210","article-title":"Dissection of the transactivation function of the transcription factor encoded by the eye developmental gene PAX6","volume":"273","author":"Tang","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1101\/gad.8.17.2022","article-title":"Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing","volume":"8","author":"Epstein","year":"1994","journal-title":"Genes Dev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8355","DOI":"10.1016\/S0021-9258(17)37201-0","article-title":"Identification of a Pax paired domain recognition sequence and evidence for DNA-dependent conformational changes","volume":"269","author":"Epstein","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1086\/302529","article-title":"Missense mutation in the alternative splice region of the PAX6 gene in eye anomalies","volume":"65","author":"Azuma","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.ydbio.2005.12.041","article-title":"Analysis of Pax6 expression using a BAC transgene reveals the presence of a paired-less isoform of Pax6 in the eye and olfactory bulb","volume":"292","author":"Kim","year":"2006","journal-title":"Dev. Biol."},{"key":"ref_35","first-page":"7257","article-title":"Characterization of quail Pax-6 (Pax-QNR) proteins expressed in the neuroretina","volume":"13","author":"Carriere","year":"1993","journal-title":"Mol. Cell. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.ydbio.2007.10.043","article-title":"Overexpression of pairedless Pax6 in the retina disrupts corneal development and affects lens cell survival","volume":"313","author":"Kim","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.ydbio.2006.08.060","article-title":"Long-range downstream enhancers are essential for Pax6 expression","volume":"299","author":"Kleinjan","year":"2006","journal-title":"Dev. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.ydbio.2007.04.015","article-title":"Mechanisms controlling Pax6 isoform expression in the retina have been conserved between teleosts and mammals","volume":"307","author":"Lakowski","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1093\/hmg\/ddi069","article-title":"The Pax6 isoform bearing an alternative spliced exon promotes the development of the neural retinal structure","volume":"14","author":"Azuma","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/ng1281","article-title":"Growth and specification of the eye are controlled independently by Eyegone and Eyeless in Drosophila melanogaster","volume":"36","author":"Dominguez","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1242\/dev.126.2.383","article-title":"Regulation of Pax6 expression is conserved between mice and flies","volume":"126","author":"Xu","year":"1999","journal-title":"Development"},{"key":"ref_42","first-page":"1","article-title":"Quantitation of PAX6 and PAX6 (5a) transcript levels in adult human lens, cornea, and monkey retina","volume":"7","author":"Zhang","year":"2001","journal-title":"Mol. Vis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.exer.2016.04.017","article-title":"PAX6: 25th anniversary and more to learn","volume":"156","author":"Cvekl","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/ng0696-141","article-title":"PAX6 missense mutation in isolated foveal hypoplasia","volume":"13","author":"Azuma","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1093\/hmg\/11.10.1161","article-title":"PAX6 in sensory development","volume":"11","author":"Williamson","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"20807","DOI":"10.1038\/srep20807","article-title":"PAX6 Isoforms, along with Reprogramming Factors, Differentially Regulate the Induction of Cornea-specific Genes","volume":"6","author":"Sasamoto","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Pinson, J., Simpson, T.I., Mason, J.O., and Price, D.J. (2006). Positive autoregulation of the transcription factor Pax6 in response to increased levels of either of its major isoforms, Pax6 or Pax6 (5a), in cultured cells. BMC Dev. Biol., 6.","DOI":"10.1186\/1471-213X-6-25"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0012-1606(03)00058-7","article-title":"Pax6 autoregulation mediated by direct interaction of Pax6 protein with the head surface ectoderm-specific enhancer of the mouse Pax6 gene","volume":"257","author":"Aota","year":"2003","journal-title":"Dev. Biol."},{"key":"ref_49","first-page":"1295","article-title":"PAX6 dosage effects on corneal development, growth, and wound healing","volume":"237","author":"Dora","year":"2008","journal-title":"Dev. Dyn. Off. Publ. Am. Assoc. Anat."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Pinson, J., Mason, J.O., Simpson, T.I., and Price, D.J. (2005). Regulation of the Pax6: Pax6 (5a) mRNA ratio in the developing mammalian brain. BMC Dev. Biol., 5.","DOI":"10.1186\/1471-213X-5-13"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1093\/nar\/gkh334","article-title":"Functional interactions between alternatively spliced forms of Pax6 in crystallin gene regulation and in haploinsufficiency","volume":"32","author":"Chauhan","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1128\/MCB.15.2.892","article-title":"Identification and characterization of a neuroretina-specific enhancer element in the quail Pax-6 (Pax-QNR) gene","volume":"15","author":"Plaza","year":"1995","journal-title":"Mol. Cell. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.1128\/MCB.15.6.3344","article-title":"Quail Pax-6 (Pax-QNR) mRNAs are expressed from two promoters used differentially during retina development and neuronal differentiation","volume":"15","author":"Plaza","year":"1995","journal-title":"Mol. Cell. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1006\/dbio.1998.9128","article-title":"Distinct cis-essential modules direct the time-space pattern of the Pax6 gene activity","volume":"205","author":"Kammandel","year":"1999","journal-title":"Dev. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3430","DOI":"10.1074\/jbc.272.6.3430","article-title":"Transcriptional regulation of the human PAX6 gene promoter","volume":"272","author":"Xu","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ydbio.2014.01.007","article-title":"A survey of ancient conserved non-coding elements in the PAX6 locus reveals a landscape of interdigitated cis-regulatory archipelagos","volume":"387","author":"Bhatia","year":"2014","journal-title":"Dev. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"McBride, D.J., Buckle, A., van Heyningen, V., and Kleinjan, D.A. (2011). DNaseI hypersensitivity and ultraconservation reveal novel, interdependent long-range enhancers at the complex Pax6 cis-regulatory region. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028616"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0925-4773(01)00646-3","article-title":"New 3\u2032 elements control Pax6 expression in the developing pretectum, neural retina and olfactory region","volume":"112","author":"Griffin","year":"2002","journal-title":"Mech. Dev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.ydbio.2003.09.011","article-title":"Conserved elements in Pax6 intron 7 involved in (auto)regulation and alternative transcription","volume":"265","author":"Kleinjan","year":"2004","journal-title":"Dev. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0925-4773(98)00057-4","article-title":"A highly conserved lens transcriptional control element from the Pax-6 gene","volume":"73","author":"Williams","year":"1998","journal-title":"Mech. Dev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/embj.201386225","article-title":"The long non-coding RNA Paupar regulates the expression of both local and distal genes","volume":"33","author":"Vance","year":"2014","journal-title":"EMBO J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3434","DOI":"10.1093\/hmg\/ddy255","article-title":"Functional characteristics of novel pancreatic Pax6 regulatory elements","volume":"27","author":"Buckle","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ravi, V., Bhatia, S., Gautier, P., Loosli, F., Tay, B.H., Tay, A., Murdoch, E., Coutinho, P., van Heyningen, V., and Brenner, S. (2013). Sequencing of Pax6 loci from the elephant shark reveals a family of Pax6 genes in vertebrate genomes, forged by ancient duplications and divergences. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003177"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4415","DOI":"10.1242\/dev.128.22.4415","article-title":"The upstream ectoderm enhancer in Pax6 has an important role in lens induction","volume":"128","author":"Dimanlig","year":"2001","journal-title":"Development"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1101\/gad.1890410","article-title":"Precise temporal control of the eye regulatory gene Pax6 via enhancer-binding site affinity","volume":"24","author":"Rowan","year":"2010","journal-title":"Genes Dev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"8719","DOI":"10.1073\/pnas.132195699","article-title":"Mutually regulated expression of Pax6 and Six3 and its implications for the Pax6 haploinsufficient lens phenotype","volume":"99","author":"Goudreau","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1111\/j.1365-2443.2007.01114.x","article-title":"PAX6 and SOX2-dependent regulation of the Sox2 enhancer N-3 involved in embryonic visual system development","volume":"12","author":"Inoue","year":"2007","journal-title":"Genes Cells Devoted Mol. Cell. Mech."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"13755","DOI":"10.1073\/pnas.240398797","article-title":"3\u2032 deletions cause aniridia by preventing PAX6 gene expression","volume":"97","author":"Lauderdale","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1101\/gad.1007602","article-title":"Meis homeoproteins directly regulate Pax6 during vertebrate lens morphogenesis","volume":"16","author":"Zhang","year":"2002","journal-title":"Genes Dev."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Antosova, B., Smolikova, J., Klimova, L., Lachova, J., Bendova, M., Kozmikova, I., Machon, O., and Kozmik, Z. (2016). The Gene Regulatory Network of Lens Induction Is Wired through Meis-Dependent Shadow Enhancers of Pax6. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006441"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Blanco-Kelly, F., Palomares, M., Vallespin, E., Villaverde, C., Martin-Arenas, R., Velez-Monsalve, C., Lorda-Sanchez, I., Nevado, J., Trujillo-Tiebas, M.J., and Lapunzina, P. (2017). Improving molecular diagnosis of aniridia and WAGR syndrome using customized targeted array-based CGH. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172363"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Ansari, M., Rainger, J., Hanson, I.M., Williamson, K.A., Sharkey, F., Harewood, L., Sandilands, A., Clayton-Smith, J., Dollfus, H., and Bitoun, P. (2016). Genetic Analysis of \u2018PAX6-Negative\u2019 Individuals with Aniridia or Gillespie Syndrome. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153757"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s12041-018-0925-9","article-title":"Aniridia due to a novel microdeletion affecting PAX6 regulatory enhancers: Case report and review of the literature","volume":"97","author":"Syrimis","year":"2018","journal-title":"J. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.diabres.2018.12.002","article-title":"Deletion distal to the PAX6 coding region reveals a novel basis for familial cosegregation of aniridia and diabetes mellitus","volume":"148","author":"Macdonald","year":"2019","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1007\/s00439-018-1940-x","article-title":"Implication of non-coding PAX6 mutations in aniridia","volume":"137","author":"Plaisancie","year":"2018","journal-title":"Hum. Genet."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1016\/j.jocn.2009.03.022","article-title":"A novel heterozygous deletion within the 3\u2019 region of the PAX6 gene causing isolated aniridia in a large family group","volume":"16","author":"Bayrakli","year":"2009","journal-title":"J. Clin. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1002\/humu.22816","article-title":"Microdeletions of ELP4 Are Associated with Language Impairment, Autism Spectrum Disorder, and Mental Retardation","volume":"36","author":"Addis","year":"2015","journal-title":"Hum. Mutat."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Tzoulaki, I., White, I.M., and Hanson, I.M. (2005). PAX6 mutations: Genotype-phenotype correlations. BMC Genet., 6.","DOI":"10.1186\/1471-2156-6-27"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.biochi.2014.10.027","article-title":"NMD: At the crossroads between translation termination and ribosome recycling","volume":"114","author":"Celik","year":"2015","journal-title":"Biochimie"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/sj.ejhg.5200940","article-title":"Screening for PAX6 gene mutations is consistent with haploinsufficiency as the main mechanism leading to various ocular defects","volume":"11","author":"Vincent","year":"2003","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"21531","DOI":"10.1074\/jbc.273.34.21531","article-title":"Truncation mutations in the transactivation region of PAX6 result in dominant-negative mutants","volume":"273","author":"Singh","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/ng1322","article-title":"Molecular mechanism for distinct neurological phenotypes conveyed by allelic truncating mutations","volume":"36","author":"Inoue","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/cge.13019","article-title":"Molecular analysis of patients with aniridia in Russian Federation broadens the spectrum of PAX6 mutations","volume":"92","author":"Vasilyeva","year":"2017","journal-title":"Clin. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1002\/ajmg.a.32209","article-title":"Genetic analysis of chromosome 11p13 and the PAX6 gene in a series of 125 cases referred with aniridia","volume":"146","author":"Robinson","year":"2008","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1111\/cge.12708","article-title":"Assessment of PAX6 alleles in 66 families with aniridia","volume":"89","author":"Bobilev","year":"2016","journal-title":"Clin. Genet."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1167\/iovs.08-2827","article-title":"Detailed ophthalmologic evaluation of 43 individuals with PAX6 mutations","volume":"50","author":"Hingorani","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1002\/humu.10163","article-title":"Missense mutations in the DNA-binding region and termination codon in PAX6","volume":"21","author":"Chao","year":"2003","journal-title":"Hum. Mutat."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1093\/hmg\/6.3.381","article-title":"Functional analysis of paired box missense mutations in the PAX6 gene","volume":"6","author":"Tang","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1203\/01.PDR.0000096455.00657.98","article-title":"PAX6 and congenital eye malformations","volume":"54","author":"Hanson","year":"2003","journal-title":"Pediatr. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1086\/375555","article-title":"Mutations of the PAX6 gene detected in patients with a variety of optic-nerve malformations","volume":"72","author":"Azuma","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ejmg.2014.05.002","article-title":"The genetic architecture of microphthalmia, anophthalmia and coloboma","volume":"57","author":"Williamson","year":"2014","journal-title":"Eur. J. Med. Genet."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Harding, P., and Moosajee, M. (2019). The Molecular Basis of Human Anophthalmia and Microphthalmia. J. Dev. Biol., 7.","DOI":"10.3390\/jdb7030016"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/ejhg.2015.155","article-title":"Novel mutations in PAX6, OTX2 and NDP in anophthalmia, microphthalmia and coloboma","volume":"24","author":"Deml","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"352","DOI":"10.3389\/fncel.2019.00352","article-title":"Beyond the Exome: The Non-coding Genome and Enhancers in Neurodevelopmental Disorders and Malformations of Cortical Development","volume":"13","author":"Perenthaler","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3630","DOI":"10.1093\/hmg\/ddx251","article-title":"Mutations of conserved non-coding elements of PITX2 in patients with ocular dysgenesis and developmental glaucoma","volume":"26","author":"Protas","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_96","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_97","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/sj.ejhg.5200308","article-title":"Mutational analysis of PAX6: 16 novel mutations including 5 missense mutations with a mild aniridia phenotype","volume":"7","author":"Gronskov","year":"1999","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1006\/mcpr.1997.0117","article-title":"Combined SSCP\/heteroduplex analysis in the screening for PAX6 mutations","volume":"11","author":"Axton","year":"1997","journal-title":"Mol. Cell. Probes"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/s41431-018-0288-y","article-title":"Functional reassessment of PAX6 single nucleotide variants by in vitro splicing assay","volume":"27","author":"Filatova","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"15052","DOI":"10.1038\/hgv.2015.52","article-title":"Genotype-phenotype correlation of PAX6 gene mutations in aniridia","volume":"3","author":"Yokoi","year":"2016","journal-title":"Hum. Genome Var."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1086\/344396","article-title":"Frequent chromosome aberrations revealed by molecular cytogenetic studies in patients with aniridia","volume":"71","author":"Crolla","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1007\/s00439-018-1934-8","article-title":"The genetic architecture of aniridia and Gillespie syndrome","volume":"138","author":"Hall","year":"2019","journal-title":"Hum. Genet."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/ng0894-463","article-title":"PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects","volume":"7","author":"Glaser","year":"1994","journal-title":"Nat. Genet."},{"key":"ref_104","first-page":"372","article-title":"Malformations of the brain in two fetuses with a compound heterozygosity for two PAX6 mutations","volume":"47","author":"Szymanska","year":"2009","journal-title":"Folia Neuropathol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1002\/ajmg.a.33081","article-title":"Compound heterozygosity for mutations in PAX6 in a patient with complex brain anomaly, neonatal diabetes mellitus, and microophthalmia","volume":"149","author":"Solomon","year":"2009","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"306","DOI":"10.3109\/08820538.2013.825293","article-title":"A review of the clinical and genetic aspects of aniridia","volume":"28","author":"Lee","year":"2013","journal-title":"Semin. Ophthalmol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.jmoldx.2016.01.002","article-title":"Detection and Quantification of Mosaic Mutations in Disease Genes by Next-Generation Sequencing","volume":"18","author":"Qin","year":"2016","journal-title":"J. Mol. Diagn."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1002\/mgg3.329","article-title":"Panel-based whole exome sequencing identifies novel mutations in microphthalmia and anophthalmia patients showing complex Mendelian inheritance patterns","volume":"5","author":"Riera","year":"2017","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1002\/mgg3.481","article-title":"Extension of the mutation spectrum of PAX6 from three Chinese congenital aniridia families and identification of male gonadal mosaicism","volume":"6","author":"Bai","year":"2018","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"479","DOI":"10.3389\/fgene.2018.00479","article-title":"Parental Mosaicism in PAX6 Causes Intra-Familial Variability: Implications for Genetic Counseling of Congenital Aniridia and Microphthalmia","volume":"9","author":"Tarilonte","year":"2018","journal-title":"Front. Genet."},{"key":"ref_111","first-page":"88","article-title":"Mutational analysis and genotype-phenotype correlations in southern Indian patients with sporadic and familial aniridia","volume":"21","author":"Dubey","year":"2015","journal-title":"Mol. Vis."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"104","DOI":"10.5301\/EJO.2011.8318","article-title":"Glaucoma and frequency of ocular and general diseases in 30 patients with aniridia: A clinical study","volume":"22","author":"Gramer","year":"2012","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1097\/ICU.0000000000000405","article-title":"PAX6 aniridia syndrome: Clinics, genetics, and therapeutics","volume":"28","author":"Lim","year":"2017","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/sj.eye.6701642","article-title":"Aniridia and optic nerve hypoplasia","volume":"19","author":"McCulley","year":"2005","journal-title":"Eye"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1167\/iovs.17-23047","article-title":"Color Vision in Aniridia","volume":"59","author":"Pedersen","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.oret.2019.01.020","article-title":"The Cone Photoreceptor Mosaic in Aniridia: Within-Family Phenotype-Genotype Discordance","volume":"3","author":"Pedersen","year":"2019","journal-title":"Ophthalmol. Retin."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Lagali, N., Wowra, B., Fries, F.N., Latta, L., Moslemani, K., Utheim, T.P., Wylegala, E., Seitz, B., and Kasmann-Kellner, B. (2019). Early phenotypic features of aniridia-associated keratopathy and association with PAX6 coding mutations. Ocul. Surf.","DOI":"10.1016\/j.jtos.2019.11.002"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Lagali, N., Wowra, B., Fries, F.N., Latta, L., Moslemani, K., Utheim, T.P., Wylegala, E., Seitz, B., and Kasmann-Kellner, B. (2019). PAX6 Mutational Status Determines Aniridia-Associated Keratopathy Phenotype. Ophthalmology.","DOI":"10.1016\/j.ophtha.2019.09.034"},{"key":"ref_119","first-page":"1305","article-title":"Run-on mutation in the PAX6 gene and chorioretinal degeneration in autosomal dominant aniridia","volume":"17","author":"Aggarwal","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1167\/iovs.08-3032","article-title":"Severe molecular defects of a novel FOXC1 W152G mutation result in aniridia","volume":"50","author":"Ito","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_121","first-page":"1231","article-title":"Asymmetric phenotype of Axenfeld-Rieger anomaly and aniridia associated with a novel PITX2 mutation","volume":"17","author":"Law","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/ceo.12152","article-title":"Genomics and anterior segment dysgenesis: A review","volume":"42","author":"Ito","year":"2014","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.bbadis.2016.10.018","article-title":"A mouse model of aniridia reveals the in vivo downstream targets of Pax6 driving iris and ciliary body development in the eye","volume":"1863","author":"Wang","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1073\/pnas.1109540109","article-title":"Forkhead box transcription factor FoxC1 preserves corneal transparency by regulating vascular growth","volume":"109","author":"Seo","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1002\/humu.22907","article-title":"Variants in TRIM44 Cause Aniridia by Impairing PAX6 Expression","volume":"36","author":"Zhang","year":"2015","journal-title":"Hum. Mutat."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1056\/NEJMoa0801119","article-title":"Brain-derived neurotrophic factor and obesity in the WAGR syndrome","volume":"359","author":"Han","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1542\/peds.2004-0467","article-title":"WAGR syndrome: A clinical review of 54 cases","volume":"116","author":"Fischbach","year":"2005","journal-title":"Pediatrics"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1002\/ajmg.a.33878","article-title":"11p14.1 microdeletions associated with ADHD, autism, developmental delay, and obesity","volume":"155","author":"Shinawi","year":"2011","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/ajmg.a.38539","article-title":"Maternal inheritance of BDNF deletion, with phenotype of obesity and developmental delay in mother and child","volume":"176","author":"Harcourt","year":"2018","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/ng1985","article-title":"Mapping autism risk loci using genetic linkage and chromosomal rearrangements","volume":"39","author":"Szatmari","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/90042","article-title":"PAX6 haploinsufficiency causes cerebral malformation and olfactory dysfunction in humans","volume":"28","author":"Sisodiya","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1097\/00019605-199407000-00012","article-title":"Obesity: A new feature of WAGR (del 11p) syndrome","volume":"3","author":"Marlin","year":"1994","journal-title":"Clin. Dysmorphol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/ajmg.10013","article-title":"Third case of WAGR syndrome with severe obesity and constitutional deletion of chromosome (11)(p12p14)","volume":"107","author":"Gul","year":"2002","journal-title":"Am. J. Med. Genet."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/ejhg.2013.162","article-title":"Autosomal-dominant nystagmus, foveal hypoplasia and presenile cataract associated with a novel PAX6 mutation","volume":"22","author":"Thomas","year":"2014","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3109\/13816810.2011.642452","article-title":"Microphthalmia, late onset keratitis, and iris coloboma\/aniridia in a family with a novel PAX6 mutation","volume":"33","author":"Xiao","year":"2012","journal-title":"Ophthalmic Genet."},{"key":"ref_136","first-page":"511","article-title":"Three new PAX6 mutations including one causing an unusual ophthalmic phenotype associated with neurodevelopmental abnormalities","volume":"13","author":"Dansault","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_137","first-page":"1855","article-title":"A case of atypical WAGR syndrome with anterior segment anomaly and microphthalmos","volume":"119","author":"Kawase","year":"2001","journal-title":"Arch. Ophthalmol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1101\/gad.887101","article-title":"Pax6 and SOX2 form a co-DNA-binding partner complex that regulates initiation of lens development","volume":"15","author":"Kamachi","year":"2001","journal-title":"Genes Dev."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Aberdam, E., Petit, I., Sangari, L., and Aberdam, D. (2017). Induced pluripotent stem cell-derived limbal epithelial cells (LiPSC) as a cellular alternative for in vitro ocular toxicity testing. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179913"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Williamson, K.A., Hall, H.N., Owen, L.J., Livesey, B.J., Hanson, I.M., Adams, G.G.W., Bodek, S., Calvas, P., Castle, B., and Clarke, M. (2019). Recurrent heterozygous PAX6 missense variants cause severe bilateral microphthalmia via predictable effects on DNA-protein interaction. Genet. Med. Off. J. Am. Coll. Med. Genet.","DOI":"10.1038\/s41436-019-0685-9"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Guo, H., Dai, L., Huang, Y., Liao, Q., and Bai, Y. (2013). A large novel deletion downstream of PAX6 gene in a Chinese family with ocular coloboma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083073"},{"key":"ref_142","first-page":"407","article-title":"Familial congenital cataract, coloboma, and nystagmus phenotype with variable expression caused by mutation in PAX6 in a South African family","volume":"24","author":"Goolam","year":"2018","journal-title":"Mol. Vis."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1136\/jmg.2004.025494","article-title":"Ocular coloboma: A reassessment in the age of molecular neuroscience","volume":"41","author":"Williams","year":"2004","journal-title":"J. Med. Genet."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.gene.2019.04.035","article-title":"A family with a mild form of congenital nystagmus and optic disc coloboma caused by a novel PAX6 mutation","volume":"705","author":"Lee","year":"2019","journal-title":"Gene"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"4325","DOI":"10.1242\/dev.127.20.4325","article-title":"Spatial specification of mammalian eye territories by reciprocal transcriptional repression of Pax2 and Pax6","volume":"127","author":"Schwarz","year":"2000","journal-title":"Development"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.ajhg.2016.03.004","article-title":"Recessive and Dominant De Novo ITPR1 Mutations Cause Gillespie Syndrome","volume":"98","author":"Gerber","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.ajhg.2016.03.018","article-title":"A Restricted Repertoire of De Novo Mutations in ITPR1 Cause Gillespie Syndrome with Evidence for Dominant-Negative Effect","volume":"98","author":"McEntagart","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1080\/13816810600976897","article-title":"Ocular findings in Gillespie-like syndrome: Association with a new PAX6 mutation","volume":"27","author":"Ticho","year":"2006","journal-title":"Ophthalmic Genet."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/ng0294-168","article-title":"Mutations at the PAX6 locus are found in heterogeneous anterior segment malformations including Peters\u2019 anomaly","volume":"6","author":"Hanson","year":"1994","journal-title":"Nat. Genet."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/(SICI)1098-1004(1998)12:5<304::AID-HUMU3>3.0.CO;2-D","article-title":"Ten novel mutations found in Aniridia","volume":"12","author":"Wolf","year":"1998","journal-title":"Hum. Mutat."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13072-016-0087-z","article-title":"Pax6 associates with H3K4-specific histone methyltransferases Mll1, Mll2, and Set1a and regulates H3K4 methylation at promoters and enhancers","volume":"9","author":"Sun","year":"2016","journal-title":"Epigenet. Chromatin"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"6827","DOI":"10.1093\/nar\/gkv589","article-title":"Identification of in vivo DNA-binding mechanisms of Pax6 and reconstruction of Pax6-dependent gene regulatory networks during forebrain and lens development","volume":"43","author":"Sun","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Tsui, S., Wang, J., Wang, L., Dai, W., and Lu, L. (2016). CTCF-Mediated and Pax6-Associated Gene Expression in Corneal Epithelial Cell-Specific Differentiation. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162071"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Ryan, B.C., Lowe, K., Hanson, L., Gil, T., Braun, L., Howard, P.L., and Chow, R.L. (2018). Mapping the Pax6 3\u2032 untranslated region microRNA regulatory landscape. BMC Genom., 19.","DOI":"10.1186\/s12864-018-5212-x"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1002\/embj.201387215","article-title":"MiR-135b is a direct PAX6 target and specifies human neuroectoderm by inhibiting TGF-beta\/BMP signaling","volume":"33","author":"Bhinge","year":"2014","journal-title":"EMBO J."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Shaham, O., Gueta, K., Mor, E., Oren-Giladi, P., Grinberg, D., Xie, Q., Cvekl, A., Shomron, N., Davis, N., and Keydar-Prizant, M. (2013). Pax6 regulates gene expression in the vertebrate lens through miR-204. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003357"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1002\/stem.1068","article-title":"Pluripotent stem cell model reveals essential roles for miR-450b-5p and miR-184 in embryonic corneal lineage specification","volume":"30","author":"Serror","year":"2012","journal-title":"Stem Cells"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"11762","DOI":"10.1038\/s41598-017-12084-1","article-title":"DNA Methylomes Reveal Biological Networks Involved in Human Eye Development, Functions and Associated Disorders","volume":"7","author":"Berdasco","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.cmet.2019.09.013","article-title":"The Long Noncoding RNA Paupar Modulates PAX6 Regulatory Activities to Promote Alpha Cell Development and Function","volume":"30","author":"Singer","year":"2019","journal-title":"Cell Metab."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature17000","article-title":"Co-ordinated ocular development from human iPS cells and recovery of corneal function","volume":"531","author":"Hayashi","year":"2016","journal-title":"Nature"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Qiu, X., Yang, J., Liu, T., Jiang, Y., Le, Q., and Lu, Y. (2012). Efficient generation of lens progenitor cells from cataract patient-specific induced pluripotent stem cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032612"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"41286","DOI":"10.1038\/srep41286","article-title":"Cornea organoids from human induced pluripotent stem cells","volume":"7","author":"Foster","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.stem.2012.05.009","article-title":"Self-formation of optic cups and storable stratified neural retina from human ESCs","volume":"10","author":"Nakano","year":"2012","journal-title":"Cell Stem Cell"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Gamm, D.M., Clark, E., Capowski, E.E., and Singh, R. (2019). The Role of FGF9 In The Production of Neural Retina And RPE In A Pluripotent Stem Cell Model of Early Human Retinal Development. Am. J. Ophthalmol.","DOI":"10.1016\/j.ajo.2019.04.033"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.stem.2016.03.021","article-title":"Identification and Correction of Mechanisms Underlying Inherited Blindness in Human iPSC-Derived Optic Cups","volume":"18","author":"Parfitt","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1056\/NEJMra1716145","article-title":"Stem Cells in the Treatment of Disease","volume":"380","author":"Blau","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/j.stemcr.2018.02.003","article-title":"Gene Correction Reverses Ciliopathy and Photoreceptor Loss in iPSC-Derived Retinal Organoids from Retinitis Pigmentosa Patients","volume":"10","author":"Deng","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.exer.2017.01.001","article-title":"Mechanism and evidence of nonsense suppression therapy for genetic eye disorders","volume":"155","author":"Richardson","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.omtn.2017.05.002","article-title":"Efficacy of Postnatal In Vivo Nonsense Suppression Therapy in a Pax6 Mouse Model of Aniridia","volume":"7","author":"Wang","year":"2017","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1172\/JCI70462","article-title":"Postnatal manipulation of Pax6 dosage reverses congenital tissue malformation defects","volume":"124","author":"Wang","year":"2014","journal-title":"J. Clin. Investig."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/10\/12\/1050\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:42:57Z","timestamp":1760190177000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/10\/12\/1050"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,17]]},"references-count":170,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["genes10121050"],"URL":"https:\/\/doi.org\/10.3390\/genes10121050","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,17]]}}}