ArticleHuman molecular genetics2017
Mutations of conserved non-coding elements of PITX2 in patients with ocular dysgenesis and developmental glaucoma.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Pooled it
- Exome-wide screening discovers novel pathogenic variants in Vietnamese primary congenital glaucoma patients.Genes & genomics · 2026Article
- Non-coding structural variants disrupting conserved PITX2 enhancer loci in Axenfeld-Rieger syndrome.European journal of human genetics : EJHG · 2026Article
- Comprehensive Analysis of Congenital Aniridia and Differential Diagnoses: Genetic Insights and Clinical Manifestations.Ophthalmology and therapy · 2025Review
- Long Noncoding RNAs Expressed in Mouse Pituitary Development and Mature Hormone-Producing Cells.Endocrinology · 2024Article
- 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
- AHuman mutation · 2024Article
- Complex genomic rearrangement with deletion ofMolecular vision · 2024Review
- Commercial Gene Panels for Congenital Anterior Segment Anomalies: Are They All the Same?American journal of ophthalmology · 2023Observational
- Diagnostic yield of next generation sequencing gene panel assays for early-onset glaucoma in an ethnically diverse population.Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus · 2022Article
- CRISPR-Cas9-mediated functional dissection of the foxc1 genomic region in zebrafish identifies critical conserved cis-regulatory elements.Human genomics · 2022Article
- Early-Onset Glaucoma inBiomedicines · 2022Article
- Zebrafish Model in Ophthalmology to Study Disease Mechanism and Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Pitx genes in development and disease.Cellular and molecular life sciences : CMLS · 2021Review
- Interpreting the impact of noncoding structural variation in neurodevelopmental disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Review
- Ocular genetics in the genomics age.American journal of medical genetics. Part C, Seminars in medical genetics · 2020Review
- Novel mutations in the PITX2 gene in Pakistani and Mexican families with Axenfeld-Rieger syndrome.Molecular genetics & genomic medicine · 2020Article
- Transcriptome analysis of neural progenitor cells derived from Lowe syndrome induced pluripotent stem cells: identification of candidate genes for the neurodevelopmental and eye manifestations.Journal of neurodevelopmental disorders · 2020Article
- A large deletion spanningMolecular vision · 2020Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
Mutations in FOXC1 and PITX2 constitute the most common causes of ocular anterior segment dysgenesis (ASD), and confer a high risk for secondary glaucoma. The genetic causes underlying ASD in approximately half of patients remain unknown, despite many of them being screened by whole exome sequencing. Here, we performed whole genome sequencing on DNA from two affected individuals from a family with dominantly inherited ASD and glaucoma to identify a 748-kb deletion in a gene desert that contains conserved putative PITX2 regulatory elements. We used CRISPR/Cas9 to delete the orthologous region in zebrafish in order to test the pathogenicity of this structural variant. Deletion in zebrafish reduced pitx2 expression during development and resulted in shallow anterior chambers. We screened additional patients for copy number variation of the putative regulatory elements and found an overlapping deletion in a second family and in a potentially-ancestrally-related index patient with ASD and glaucoma. These data suggest that mutations affecting conserved non-coding elements of PITX2 may constitute an important class of mutations in patients with ASD for whom the molecular cause of their disease have not yet been identified. Improved functional annotation of the human genome and transition to sequencing of patient genomes instead of exomes will be required before the magnitude of this class of mutations is fully understood.
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Registered trials
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.