ReviewAmerican journal of human genetics2013
Disruption of autoregulatory feedback by a mutation in a remote, ultraconserved PAX6 enhancer causes aniridia.
Review in American journal of human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 203 citations in OpenAlex.
- Mechanisms underlying disease-causing variants in promoters and enhancers.Nature genetics · 2026Review
- Continuous negative autoregulation fine-tunes dosage-sensitive transcription factor expression to maintain post-mitotic neuron identity.bioRxiv : the preprint server for biology · 2026Article
- So Fragile, So Human: Noncoding DNA Regions Orchestrating Gene Expression Involved in Neurodevelopmental Disorders and in Human Brain Evolution.International journal of molecular sciences · 2026Review
- Enhancer Trajectories in Lineage Commitment: Regulatory Logic of States and Cooperation.Biomolecules · 2026Review
- A structure-guided approach to noncoding variant evaluation for transcription factor binding using AlphaFold 3.Nucleic acids research · 2026Article
- EnhancerMatcher: comparing cell-type-specific enhancer activity of DNA sequences using deep convolutional neural networks and explainable AI.NAR genomics and bioinformatics · 2025Article
- Gene Dosage Sensitivity and Human Genetic Diseases.Journal of inherited metabolic disease · 2025Review
- Comprehensive Analysis of Congenital Aniridia and Differential Diagnoses: Genetic Insights and Clinical Manifestations.Ophthalmology and therapy · 2025Review
- The mutational landscape and functional effects of noncoding ultraconserved elements in human cancers.Science advances · 2025Article
- Putative looping factor ZNF143/ZFP143 is an essential transcriptional regulator with no looping function.Molecular cell · 2025Article
- Functional associations of evolutionarily recent human genes exhibit sensitivity to the 3D genome landscape and disease.bioRxiv : the preprint server for biology · 2024Article
- Deletion upstream of MAB21L2 highlights the importance of evolutionarily conserved non-coding sequences for eye development.Nature communications · 2024Article
- A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders.Nature communications · 2024Article
- Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms.Progress in retinal and eye research · 2024Review
- Deep mutational scanning quantifies DNA binding and predicts clinical outcomes of PAX6 variants.Molecular systems biology · 2024Article
- A bird's eye view on the use of whole exome sequencing in rare congenital ophthalmic diseases.Journal of human genetics · 2024Article
- Stochasticity in genetics and gene regulation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Functional categorization of gene regulatory variants that cause Mendelian conditions.Human genetics · 2024Review
- Structural Variant Disrupting the Expression of the RemoteInternational journal of molecular sciences · 2024Article
- Multi-omics analysis in human retina uncovers ultraconserved cis-regulatory elements at rare eye disease loci.Nature communications · 2024Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
The strictly regulated expression of most pleiotropic developmental control genes is critically dependent on the activity of long-range cis-regulatory elements. This was revealed by the identification of individuals with a genetic condition lacking coding-region mutations in the gene commonly associated with the disease but having a variety of nearby chromosomal abnormalities, collectively described as cis-ruption disease cases. The congenital eye malformation aniridia is caused by haploinsufficiency of the developmental regulator PAX6. We discovered a de novo point mutation in an ultraconserved cis-element located 150 kb downstream from PAX6 in an affected individual with intact coding region and chromosomal locus. The element SIMO acts as a strong enhancer in developing ocular structures. The mutation disrupts an autoregulatory PAX6 binding site, causing loss of enhancer activity, resulting in defective maintenance of PAX6 expression. These findings reveal a distinct regulatory mechanism for genetic disease by disruption of an autoregulatory feedback loop critical for maintenance of gene expression through development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.