SynthesisGenetics in medicine : official journal of the American College of Medical Genetics2022
Identification of 4 novel human ocular coloboma genes ANK3, BMPR1B, PDGFRA, and CDH4 through evolutionary conserved vertebrate gene analysis.
Synthesis in Genetics in medicine : official journal of the American College of Medical Genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Transgene-Induced Chromosomal Rearrangement With Aberrant Human Vascular Endothelial Growth Factor at the Optic Fissure Leads to Uveal Coloboma in Mice.Investigative ophthalmology & visual science · 2025Observational
- Machine Learning Identifies Key Gene Markers Related to Fetal Retina Development at Single-Cell Transcription Level.Investigative ophthalmology & visual science · 2025Article
- A Novel De Novo Missense Variant in Netrin-1 (NTN1) Associated With Chorioretinal Coloboma, Sensorineural Hearing Loss and Polydactyly.Clinical genetics · 2025Article
- Gene and phenome-based analysis of the shared genetic architecture of eye diseases.American journal of human genetics · 2025Article
- Holoprosencephaly and cyclopia inAnimal cells and systems · 2025Article
- High Clinical Exome Sequencing Diagnostic Rates and Novel Phenotypic Expansions for Nonisolated Microphthalmia, Anophthalmia, and Coloboma.Investigative ophthalmology & visual science · 2024Article
- Genome-wide association identifies novel ROP risk loci in a multiethnic cohort.Communications biology · 2024Article
- Identification of the regulatory circuit governing corneal epithelial fate determination and disease.PLoS biology · 2023Article
- Identification of Novel Coloboma Candidate Genes through Conserved Gene Expression Analyses across Four Vertebrate Species.Biomolecules · 2023Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeOcular coloboma arises from genetic or environmental perturbations that inhibit optic fissure (OF) fusion during early eye development. Despite high genetic heterogeneity, 70% to 85% of patients remain molecularly undiagnosed. In this study, we have identified new potential causative genes using cross-species comparative meta-analysis.
methodsEvolutionarily conserved differentially expressed genes were identified through in silico analysis, with in situ hybridization, gene knockdown, and rescue performed to confirm spatiotemporal gene expression and phenotype. Interrogation of the 100,000 Genomes Project for putative pathogenic variants was performed.
resultsNine conserved differentially expressed genes between zebrafish and mouse were identified. Expression of zebrafish ank3a, bmpr1ba/b, cdh4, and pdgfaa was localized to the OF, periocular mesenchyme cells, or ciliary marginal zone, regions traversed by the OF. Knockdown of ank3, bmpr1b, and pdgfaa revealed a coloboma and/or microphthalmia phenotype. Novel pathogenic variants in ANK3, BMPR1B, PDGFRA, and CDH4 were identified in 8 unrelated coloboma families. We showed BMPR1B rescued the knockdown phenotype but variant messenger RNAs failed, providing evidence of pathogenicity.
conclusionWe show the utility of cross-species meta-analysis to identify several novel coloboma disease-causing genes. There is a potential to increase the diagnostic yield for new and unsolved patients while adding to our understanding of the genetic basis of OF morphogenesis.
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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 Socratic graph.