ArticleHuman molecular genetics2015
A role for repressive complexes and H3K9 di-methylation in PRDM5-associated brittle cornea syndrome.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Vascular phenotypes in nonvascular subtypes of the Ehlers-Danlos syndrome: a systematic review.Genetics in medicine : official journal of the American College of Medical Genetics · 2018Pooled it
- Identification of Cell Fate Determining Transcription Factors for Generating Brain Endothelial Cells.Stem cell reviews and reports · 2025Article
- Brittle cornea syndrome: A novel mutation.Heliyon · 2024Article
- Methylation in cornea and corneal diseases: a systematic review.Cell death discovery · 2024Review
- OiScience · 2024Article
- A mouse model of brittle cornea syndrome caused by mutation in Zfp469.Disease models & mechanisms · 2021Article
- Review
- Case report of aIndian journal of ophthalmology · 2020Article
- PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus.Scientific reports · 2019Article
- Systematic review of differential methylation in rare ophthalmic diseases.BMJ open ophthalmology · 2019Review
- Brittle cornea syndrome: current perspectives.Clinical ophthalmology (Auckland, N.Z.) · 2019Article
- Identification of Prdm genes in human corneal endothelium.Experimental eye research · 2017Article
Corrections and comments
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Authors and funding
13 authors at 8 institutions in 5 countries.
Funding
Abstract
Type 2 brittle cornea syndrome (BCS2) is an inherited connective tissue disease with a devastating ocular phenotype caused by mutations in the transcription factor PR domain containing 5 (PRDM5) hypothesized to exert epigenetic effects through histone and DNA methylation. Here we investigate clinical samples, including skin fibroblasts and retinal tissue from BCS2 patients, to elucidate the epigenetic role of PRDM5 and mechanisms of its dysregulation in disease. First we report abnormal retinal vascular morphology in the eyes of two cousins with BCS2 (PRDM5 Δ exons 9-14) using immunohistochemistry, and mine data from skin fibroblast expression microarrays from patients with PRDM5 mutations p.Arg590* and Δ exons 9-14, as well as from a PRDM5 ChIP-sequencing experiment. Gene ontology analysis of dysregulated PRDM5-target genes reveals enrichment for extracellular matrix (ECM) genes supporting vascular integrity and development. Q-PCR and ChIP-qPCR confirm upregulation of critical mediators of ECM stability in vascular structures (COL13A1, COL15A1, NTN1, CDH5) in patient fibroblasts. We identify H3K9 di-methylation (H3K9me2) at these PRDM5-target genes in fibroblasts, and demonstrate that the BCS2 mutation p.Arg83Cys diminishes interaction of PRDM5 with repressive complexes, including NuRD complex protein CHD4, and the repressive chromatin interactor HP1BP3, by co-immunoprecipitation combined with mass spectrometry. We observe reduced heterochromatin protein 1 binding protein 3 (HP1BP3) staining in the retinas of two cousins lacking exons 9-14 by immunohistochemistry, and dysregulated H3K9me2 in skin fibroblasts of three patients (p.Arg590*, p.Glu134* and Δ exons 9-14) by western blotting. These findings suggest that defective interaction of PRDM5 with repressive complexes, and dysregulation of H3K9me2, play a role in PRDM5-associated disease.
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Registered trials
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