{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:50:40Z","timestamp":1790833840752,"version":"4.1.0"},"reference-count":45,"publisher":"Hindawi Limited","issue":"10","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1454,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hum. Mutat."],"published-print":{"date-parts":[[2011,10]]},"DOI":"10.1002\/humu.21550","type":"journal-article","created":{"date-parts":[[2011,8,11]],"date-time":"2011-08-11T14:03:48Z","timestamp":1313071428000},"page":"1144-1152","source":"Crossref","is-referenced-by-count":40,"title":["Digenic inheritance of mutations in FOXC1 and PITX2\u2009: Correlating transcription factor function and axenfeld-rieger disease severity"],"prefix":"10.1155","volume":"32","author":[{"given":"Daniel","family":"Kelberman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Holder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Jacques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Calvas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoul C.","family":"Hennekam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken K.","family":"Nischal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane C.","family":"Sowden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"98","published-online":{"date-parts":[[2011,9,8]]},"reference":[{"key":"10.1002\/humu.21550-BIB1|cit1","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat Methods"},{"key":"10.1002\/humu.21550-BIB2|cit2","doi-asserted-by":"crossref","first-page":"7001","DOI":"10.1128\/MCB.19.10.7001","article-title":"Multifunctional role of the Pitx2 homeodomain protein C-terminal tail","volume":"19","author":"Amendt","year":"1999","journal-title":"Mol Cell Biol"},{"key":"10.1002\/humu.21550-BIB3|cit3","doi-asserted-by":"crossref","first-page":"4905","DOI":"10.1167\/iovs.06-0457","article-title":"Reduced human and murine corneal thickness in an Axenfeld-Rieger syndrome subtype","volume":"47","author":"Asai-Coakwell","year":"2006","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1002\/humu.21550-BIB4|cit4","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1093\/hmg\/ddl008","article-title":"Functional interactions between FOXC1 and PITX2 underlie the sensitivity to FOXC1 gene dose in Axenfeld-Rieger syndrome and anterior segment dysgenesis","volume":"15","author":"Berry","year":"2006","journal-title":"Hum Mol Genet"},{"key":"10.1002\/humu.21550-BIB5|cit5","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1093\/hmg\/ddm326","article-title":"FOXC1 is required for cell viability and resistance to oxidative stress in the eye through the transcriptional regulation of FOXO1A","volume":"17","author":"Berry","year":"2008","journal-title":"Hum Mol Genet"},{"key":"10.1002\/humu.21550-BIB6|cit6","doi-asserted-by":"crossref","first-page":"25001","DOI":"10.1074\/jbc.M201737200","article-title":"Differential regulation of gene expression by PITX2 isoforms","volume":"277","author":"Cox","year":"2002","journal-title":"J Biol Chem"},{"key":"10.1002\/humu.21550-BIB7|cit7","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1167\/iovs.10-5309","article-title":"Molecular analysis in a large cohort of patients with anterior segment malformations: expanding the spectrum of FOXC1 and PITX2 mutations and copy number changes","volume":"52","author":"D'haene","year":"2010","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1002\/humu.21550-BIB8|cit8","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1111\/j.1399-0004.2007.00879.x","article-title":"Cytogenetically invisible microdeletions involving PITX2 in Rieger syndrome","volume":"72","author":"Engenheiro","year":"2007","journal-title":"Clin Genet"},{"key":"10.1002\/humu.21550-BIB9|cit9","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1167\/iovs.08-3251","article-title":"Analysis of mutations of the PITX2 transcription factor found in patients with Axenfeld-Rieger syndrome","volume":"50","author":"Footz","year":"2009","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1002\/humu.21550-BIB10|cit10","doi-asserted-by":"crossref","first-page":"4643","DOI":"10.1242\/dev.126.20.4643","article-title":"Dosage requirement of Pitx2 for development of multiple organs","volume":"126","author":"Gage","year":"1999","journal-title":"Development"},{"key":"10.1002\/humu.21550-BIB11|cit11","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1038\/sj.ejhg.5201826","article-title":"Inherited PAX6, NF1 and OTX2 mutations in a child with microphthalmia and aniridia","volume":"15","author":"Henderson","year":"2007","journal-title":"Eur J Hum Genet"},{"key":"10.1002\/humu.21550-BIB12|cit12","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1083\/jcb.152.3.545","article-title":"PITX2 regulates procollagen lysyl hydroxylase (PLOD) gene expression: implications for the pathology of Rieger syndrome","volume":"152","author":"Hjalt","year":"2001","journal-title":"J Cell Biol"},{"key":"10.1002\/humu.21550-BIB13|cit13","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/S0002-9394(02)02061-5","article-title":"A family with Axenfeld-Rieger syndrome and Peters Anomaly caused by a point mutation (Phe112Ser) in the FOXC1 gene","volume":"135","author":"Honkanen","year":"2003","journal-title":"Am J Ophthalmol"},{"key":"10.1002\/humu.21550-BIB14|cit14","doi-asserted-by":"crossref","first-page":"228-231","DOI":"10.1038\/ng1192-228","article-title":"A homozygous stop codon in the lysyl hydroxylase gene in two siblings with Ehlers-Danlos syndrome type VI","volume":"2","author":"Hyland","year":"1992","journal-title":"Nat Genet"},{"key":"10.1002\/humu.21550-BIB15|cit15","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/ajmg.b.30237","article-title":"A novel homeobox mutation in the PITX2 gene in a family with Axenfeld-Rieger syndrome associated with brain, ocular, and dental phenotypes","volume":"141B","author":"Idrees","year":"2006a","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"10.1002\/humu.21550-BIB16|cit16","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.survophthal.2006.02.006","article-title":"A review of anterior segment dysgeneses","volume":"51","author":"Idrees","year":"2006b","journal-title":"Surv Ophthalmol"},{"key":"10.1002\/humu.21550-BIB17|cit17","doi-asserted-by":"crossref","first-page":"5749","DOI":"10.1242\/dev.126.24.5749","article-title":"Mouse Pitx2 deficiency leads to anomalies of the ventral body wall, heart, extra- and periocular mesoderm and right pulmonary isomerism","volume":"126","author":"Kitamura","year":"1999","journal-title":"Development"},{"key":"10.1002\/humu.21550-BIB18|cit18","first-page":"43","article-title":"Mutation spectrum of FOXC1 and clinical genetic heterogeneity of Axenfeld-Rieger anomaly in India","volume":"9","author":"Komatireddy","year":"2003","journal-title":"Mol Vis"},{"key":"10.1002\/humu.21550-BIB19|cit19","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1093\/hmg\/9.14.2131","article-title":"Variation in residual PITX2 activity underlies the phenotypic spectrum of anterior segment developmental disorders","volume":"9","author":"Kozlowski","year":"2000","journal-title":"Hum Mol Genet"},{"key":"10.1002\/humu.21550-BIB20|cit20","first-page":"1843","article-title":"Ocular developmental abnormalities and glaucoma associated with interstitial 6p25 duplications and deletions","volume":"43","author":"Lehmann","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1002\/humu.21550-BIB21|cit21","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/S0002-9297(07)62943-7","article-title":"Chromosomal duplication involving the forkhead transcription factor gene FOXC1 causes iris hypoplasia and glaucoma","volume":"67","author":"Lehmann","year":"2000","journal-title":"Am J Hum Genet"},{"key":"10.1002\/humu.21550-BIB22|cit22","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0168-9525(03)00111-2","article-title":"Fox's in development and disease","volume":"19","author":"Lehmann","year":"2003","journal-title":"Trends Genet"},{"key":"10.1002\/humu.21550-BIB23|cit23","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1006\/geno.1996.0177","article-title":"The I.M.A.G.E. Consortium: an integrated molecular analysis of genomes and their expression","volume":"33","author":"Lennon","year":"1996","journal-title":"Genomics"},{"key":"10.1002\/humu.21550-BIB24|cit24","doi-asserted-by":"crossref","first-page":"e1000947","DOI":"10.1371\/journal.pgen.1000947","article-title":"Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness","volume":"6","author":"Lu","year":"2010","journal-title":"PLoS Genet"},{"key":"10.1002\/humu.21550-BIB25|cit25","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nrm1310","article-title":"Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics","volume":"5","author":"Maquat","year":"2004","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1002\/humu.21550-BIB26|cit26","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1242\/jcs.01701","article-title":"Nonsense-mediated mRNA decay in mammals","volume":"118","author":"Maquat","year":"2005","journal-title":"J Cell Sci"},{"key":"10.1002\/humu.21550-BIB27|cit27","first-page":"139","article-title":"[Localization of the PITX2 gene expression in human eye cells in the course of prenatal development]","volume":"35","author":"Markintantova","year":"2008","journal-title":"Izv Akad Nauk Ser Biol"},{"key":"10.1002\/humu.21550-BIB28|cit28","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1086\/302109","article-title":"Mutations of the forkhead\/winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly","volume":"63","author":"Mears","year":"1998","journal-title":"Am J Hum Genet"},{"key":"10.1002\/humu.21550-BIB29|cit29","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1086\/344412","article-title":"Multiple hits during early embryonic development: digenic diseases and holoprosencephaly","volume":"71","author":"Ming","year":"2002","journal-title":"Am J Hum Genet"},{"key":"10.1002\/humu.21550-BIB30|cit30","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/00145756-200306000-00015","article-title":"Pediatric keratoplasty","volume":"1","author":"Nischal","year":"2003","journal-title":"Tech Ophthalmol"},{"key":"10.1002\/humu.21550-BIB31|cit31","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1086\/318183","article-title":"A spectrum of FOXC1 mutations suggests gene dosage as a mechanism for developmental defects of the anterior chamber of the eye","volume":"68","author":"Nishimura","year":"2001","journal-title":"Am J Hum Genet"},{"key":"10.1002\/humu.21550-BIB32|cit32","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/493","article-title":"The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25","volume":"19","author":"Nishimura","year":"1998","journal-title":"Nat Genet"},{"key":"10.1002\/humu.21550-BIB33|cit33","first-page":"2456","article-title":"Phenotypic variability and asymmetry of Rieger syndrome associated with PITX2 mutations","volume":"41","author":"Perveen","year":"2000","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1002\/humu.21550-BIB34|cit34","first-page":"613","article-title":"A second locus for Rieger syndrome maps to chromosome 13q14","volume":"59","author":"Phillips","year":"1996","journal-title":"Am J Hum Genet"},{"key":"10.1002\/humu.21550-BIB35|cit35","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1086\/318792","article-title":"Analyses of the effects that disease-causing missense mutations have on the structure and function of the winged-helix protein FOXC1","volume":"68","author":"Saleem","year":"2001","journal-title":"Am J Hum Genet"},{"key":"10.1002\/humu.21550-BIB36|cit36","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1093\/hmg\/ddg324","article-title":"Structural and functional analyses of disease-causing missense mutations in the forkhead domain of FOXC1","volume":"12","author":"Saleem","year":"2003","journal-title":"Hum Mol Genet"},{"key":"10.1002\/humu.21550-BIB37|cit37","doi-asserted-by":"crossref","first-page":"4182","DOI":"10.1093\/nar\/gkh742","article-title":"Essential structural and functional determinants within the forkhead domain of FOXC1","volume":"32","author":"Saleem","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"10.1002\/humu.21550-BIB38|cit38","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/ng1296-392","article-title":"Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome","volume":"14","author":"Semina","year":"1996","journal-title":"Nat Genet"},{"key":"10.1002\/humu.21550-BIB39|cit39","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1038\/sj.eye.6702852","article-title":"Molecular and developmental mechanisms of anterior segment dysgenesis","volume":"21","author":"Sowden","year":"2007","journal-title":"Eye"},{"key":"10.1002\/humu.21550-BIB40|cit40","doi-asserted-by":"crossref","first-page":"198","DOI":"10.3928\/0191-3913-19870701-12","article-title":"The Rieger syndrome and a chromosome 13 deletion","volume":"24","author":"Stathacopoulos","year":"1987","journal-title":"J Pediatr Ophthalmol Strabismus"},{"key":"10.1002\/humu.21550-BIB41|cit41","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1167\/iovs.06-0472","article-title":"Genotype-phenotype correlations in Axenfeld-Rieger malformation and glaucoma patients with FOXC1 and PITX2 mutations","volume":"48","author":"Strungaru","year":"2007","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1002\/humu.21550-BIB42|cit42","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1038\/ejhg.2009.93","article-title":"Axenfeld-Rieger syndrome and spectrum of PITX2 and FOXC1 mutations","volume":"17","author":"Tumer","year":"2009","journal-title":"Eur J Hum Genet"},{"key":"10.1002\/humu.21550-BIB43|cit43","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0039-6257(75)90034-X","article-title":"Anterior chamber cleavage syndrome. A stepladder classification","volume":"20","author":"Waring","year":"1975","journal-title":"Surv Ophthalmol"},{"key":"10.1002\/humu.21550-BIB44|cit44","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/(SICI)1096-8628(19970627)70:4<371::AID-AJMG8>3.0.CO;2-W","article-title":"A small deletion of 16q23.1->16q24.2 [del(16)(q23.1q24.2).ish del(16)(q23.1q24.2)(D16S395+, D16S348-, P5432+)] in a boy with iris coloboma and minor anomalies","volume":"70","author":"Werner","year":"1997","journal-title":"Am J Med Genet"},{"key":"10.1002\/humu.21550-BIB45|cit45","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1006\/mgme.2000.3076","article-title":"Mutations in the lysyl hydroxylase 1 gene that result in enzyme deficiency and the clinical phenotype of Ehlers-Danlos syndrome type VI","volume":"71","author":"Yeowell","year":"2000","journal-title":"Mol Genet Metab"}],"container-title":["Human Mutation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhumu.21550","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/onlinelibrary.wiley.com\/wol1\/doi\/10.1002\/humu.21550\/fullpdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T16:54:26Z","timestamp":1672332866000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/humu.21550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,9,8]]},"references-count":45,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2011,10]]}},"URL":"https:\/\/doi.org\/10.1002\/humu.21550","relation":{},"ISSN":["1059-7794"],"issn-type":[{"value":"1059-7794","type":"print"}],"subject":[],"published":{"date-parts":[[2011,9,8]]}}}