ArticleAmerican journal of human genetics2022
Multi-omics approach dissects cis-regulatory mechanisms underlying North Carolina macular dystrophy, a retinal enhanceropathy.
Article in American journal of human genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- A Review of PRDM13 Transcriptional Regulation in Vertebrate Retinal Development and Disease.Investigative ophthalmology & visual science · 2026Review
- Revisiting retinal and macular degeneration in the genomics era.Nature reviews. Genetics · 2026Review
- Identification of a Duplication in the RP17 Locus in an Individual With Pathogenic CEP290 Variants: Implications for RP17 Variant Classification.Investigative ophthalmology & visual science · 2026Article
- De novo and inherited dominant variants in U4 and U6 snRNA genes cause retinitis pigmentosa.Nature genetics · 2026Article
- Elucidating photoreceptor gene function with in-vivo CRISPR knock-out perturbation assay.Research square · 2025Article
- Hidden in the Genome: The First Italian Family with North Carolina Macular Dystrophy Carrying a NovelBiomedicines · 2025Article
- A zinc finger-dependent, PRDM13-driven mechanism regulates retinal progenitor cell fate from mouse embryonic stem cells via WNT signaling.Stem cell reports · 2025Article
- Genetics and diagnostics of inherited retinal diseases in the era of whole genome sequencing.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025Article
- Inter-chromosomal insertions at Xq27.1 associated with retinal dystrophy induce dysregulation of LINC00632 and CDR1as/ciRS-7.American journal of human genetics · 2025Article
- De novo and inherited dominant variants in U4 and U6 snRNAs cause retinitis pigmentosa.medRxiv : the preprint server for health sciences · 2025Article
- Systematic review:Frontiers in medicine · 2025Review
- North Carolina Macular Dystrophy.Advances in experimental medicine and biology · 2025Review
- Deletion upstream of MAB21L2 highlights the importance of evolutionarily conserved non-coding sequences for eye development.Nature communications · 2024Article
- Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression.American journal of human genetics · 2024Article
- Comparative 3D genome analysis between neural retina and retinal pigment epithelium reveals differential cis-regulatory interactions at retinal disease loci.Genome biology · 2024Article
- Utilizing systems genetics to enhance understanding into molecular targets of skin cancer.Experimental dermatology · 2024Review
- Multi-omics analysis in human retina uncovers ultraconserved cis-regulatory elements at rare eye disease loci.Nature communications · 2024Article
- Combining a prioritization strategy and functional studies nominates 5'UTR variants underlying inherited retinal disease.Genome medicine · 2024Article
- Two novel non-coding single nucleotide variants in the DNase1 hypersensitivity site ofMolecular vision · 2024Article
- A novelMolecular vision · 2024Article
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Authors and funding
29 authors at 14 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
North Carolina macular dystrophy (NCMD) is a rare autosomal-dominant disease affecting macular development. The disease is caused by non-coding single-nucleotide variants (SNVs) in two hotspot regions near PRDM13 and by duplications in two distinct chromosomal loci, overlapping DNase I hypersensitive sites near either PRDM13 or IRX1. To unravel the mechanisms by which these variants cause disease, we first established a genome-wide multi-omics retinal database, RegRet. Integration of UMI-4C profiles we generated on adult human retina then allowed fine-mapping of the interactions of the PRDM13 and IRX1 promoters and the identification of eighteen candidate cis-regulatory elements (cCREs), the activity of which was investigated by luciferase and Xenopus enhancer assays. Next, luciferase assays showed that the non-coding SNVs located in the two hotspot regions of PRDM13 affect cCRE activity, including two NCMD-associated non-coding SNVs that we identified herein. Interestingly, the cCRE containing one of these SNVs was shown to interact with the PRDM13 promoter, demonstrated in vivo activity in Xenopus, and is active at the developmental stage when progenitor cells of the central retina exit mitosis, suggesting that this region is a PRDM13 enhancer. Finally, mining of single-cell transcriptional data of embryonic and adult retina revealed the highest expression of PRDM13 and IRX1 when amacrine cells start to synapse with retinal ganglion cells, supporting the hypothesis that altered PRDM13 or IRX1 expression impairs interactions between these cells during retinogenesis. Overall, this study provides insight into the cis-regulatory mechanisms of NCMD and supports that this condition is a retinal enhanceropathy.
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