ArticleInvestigative ophthalmology & visual science2011
Potential novel mechanism for Axenfeld-Rieger syndrome: deletion of a distant region containing regulatory elements of PITX2.
Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Reassessing forebrain organization: recent evidence challenges the prosomere model.Current opinion in genetics & development · 2026Review
- Non-coding structural variants disrupting conserved PITX2 enhancer loci in Axenfeld-Rieger syndrome.European journal of human genetics : EJHG · 2026Article
- Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms.Progress in retinal and eye research · 2024Review
- Complex balanced intrachromosomal rearrangement involving PITX2 identified as a cause of Axenfeld-Rieger Syndrome.American journal of medical genetics. Part A · 2024Article
- Intergenic sequences harboring potential enhancer elements contribute to Axenfeld-Rieger syndrome by regulating PITX2.JCI insight · 2024Article
- Functional categorization of gene regulatory variants that cause Mendelian conditions.Human genetics · 2024Review
- AHuman mutation · 2024Article
- Complex genomic rearrangement with deletion ofMolecular vision · 2024Review
- CRISPR-Cas9-mediated functional dissection of the foxc1 genomic region in zebrafish identifies critical conserved cis-regulatory elements.Human genomics · 2022Article
- Mechanistic Insights into Axenfeld-Rieger Syndrome from ZebrafishInternational journal of molecular sciences · 2021Review
- AnnotSV and knotAnnotSV: a web server for human structural variations annotations, ranking and analysis.Nucleic acids research · 2021Article
- Ocular genetics in the genomics age.American journal of medical genetics. Part C, Seminars in medical genetics · 2020Review
- Spatiotemporal Characterization of Anterior Segment Mesenchyme Heterogeneity During Zebrafish Ocular Anterior Segment Development.Frontiers in cell and developmental biology · 2020Article
- Pilot GWAS of caries in African-Americans shows genetic heterogeneity.BMC oral health · 2019Article
- Genetics of anophthalmia and microphthalmia. Part 1: Non-syndromic anophthalmia/microphthalmia.Human genetics · 2019Review
- Relationship between neural crest cell specification and rare ocular diseases.Journal of neuroscience research · 2019Review
- Enhancers: bridging the gap between gene control and human disease.Human molecular genetics · 2018Review
- PITX2 deficiency and associated human disease: insights from the zebrafish model.Human molecular genetics · 2018Article
- Mutations of conserved non-coding elements of PITX2 in patients with ocular dysgenesis and developmental glaucoma.Human molecular genetics · 2017Article
- Case report of homozygous deletion involving the first coding exons of GCNT2 isoforms A and B and part of the upstream region of TFAP2A in congenital cataract.BMC medical genetics · 2016Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
purposeMutations in PITX2 are associated with Axenfeld-Rieger syndrome (ARS), which involves ocular, dental, and umbilical abnormalities. Identification of cis-regulatory elements of PITX2 is important to better understand the mechanisms of disease.
methodsConserved noncoding elements surrounding PITX2/pitx2 were identified and examined through transgenic analysis in zebrafish; expression pattern was studied by in situ hybridization. Patient samples were screened for deletion/duplication of the PITX2 upstream region using arrays and probes.
resultsZebrafish pitx2 demonstrates conserved expression during ocular and craniofacial development. Thirteen conserved noncoding sequences positioned within a gene desert as far as 1.1 Mb upstream of the human PITX2 gene were identified; 11 have enhancer activities consistent with pitx2 expression. Ten elements mediated expression in the developing brain, four regions were active during eye formation, and two sequences were associated with craniofacial expression. One region, CE4, located approximately 111 kb upstream of PITX2, directed a complex pattern including expression in the developing eye and craniofacial region, the classic sites affected in ARS. Screening of ARS patients identified an approximately 7600-kb deletion that began 106 to 108 kb upstream of the PITX2 gene, leaving PITX2 intact while removing regulatory elements CE4 to CE13.
conclusionsThese data suggest the presence of a complex distant regulatory matrix within the gene desert located upstream of PITX2 with an essential role in its activity and provides a possible mechanism for the previous reports of ARS in patients with balanced translocations involving the 4q25 region upstream of PITX2 and the current patient with an upstream deletion.
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