ArticlePloS one2015
Hypo- and hypermorphic FOXC1 mutations in dominant glaucoma: transactivation and phenotypic variability.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Pooled it
- Genetic Basis of Non-Syndromic Childhood Glaucoma Associated with Anterior Segment Dysgenesis: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Identification and functional study of a novel FOXC1 missense mutation in a Chinese family with Axenfeld-Rieger syndrome.Scientific reports · 2025Article
- Shikonin as a therapeutic agent in renal cell carcinoma: insights from TEK-related causal association with glaucoma.Frontiers in pharmacology · 2025Article
- Diagnostic Challenges of Axenfeld-Rieger Syndrome and a Novel FOXC1 Gene Mutation in a Polish Family.Journal of clinical medicine · 2024Article
- Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms.Progress in retinal and eye research · 2024Review
- The Increased Burden of Rare Variants in Four Matrix Metalloproteinase-Related Genes in Childhood Glaucoma Suggests a Complex Genetic Inheritance of the Disease.International journal of molecular sciences · 2024Article
- CRISPR-Cas9-mediated functional dissection of the foxc1 genomic region in zebrafish identifies critical conserved cis-regulatory elements.Human genomics · 2022Article
- CPAMD8 loss-of-function underlies non-dominant congenital glaucoma with variable anterior segment dysgenesis and abnormal extracellular matrix.Human genetics · 2020Article
- Disruption of foxc1 genes in zebrafish results in dosage-dependent phenotypes overlapping Axenfeld-Rieger syndrome.Human molecular genetics · 2020Article
- Axenfeld-Rieger syndrome-associated mutants of the transcription factor FOXC1 abnormally regulateThe Journal of biological chemistry · 2020Article
- Exome Sequencing in a Swiss Childhood Glaucoma Cohort RevealsTranslational vision science & technology · 2020Article
- Role ofGenes · 2020Article
- Role of FOXC2 and PITX2 rare variants associated with mild functional alterations as modifier factors in congenital glaucoma.PloS one · 2019Article
- FOXC1, the new player in the cancer sandbox.Oncotarget · 2018Review
- Glaucoma spectrum and age-related prevalence of individuals with FOXC1 and PITX2 variants.European journal of human genetics : EJHG · 2017Article
- Whole-Exome Sequencing of Congenital Glaucoma Patients Reveals Hypermorphic Variants in GPATCH3, a New Gene Involved in Ocular and Craniofacial Development.Scientific reports · 2017Article
- Rare FOXC1 variants in congenital glaucoma: identification of translation regulatory sequences.European journal of human genetics : EJHG · 2016Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dominant glaucoma, a heterogeneous, infrequent and irreversible optic neuropathy, is often associated with elevated intraocular pressure and early-onset. The role of FOXC1 in this type of glaucoma was investigated in twelve Spanish probands via nucleotide variation screening of its proximal promoter and unique exon. Functional evaluations of the identified variants included analyses of the transcriptional activity, protein stability, DNA binding ability and subcellular localization. Four different mutations that were identified in four probands (33.3%) were associated with remarkable phenotypic variability and were functionally classified as either hypermorphic (p.Y47X, p.Q106X and p.G447_G448insDG) or hypomorphic (p.I126S) alleles. To the best of our knowledge, three of the variants are novel (p.Y47X, p.I126S and p.G447_G448insDG) and, in addition, hypermorphic FOXC1 mutations are reported herein for the first time. The presence of an intact N-terminal activation domain in the truncated proteins p.Y47X and p.Q106X may underlie their associated transactivation hyperactivity by a gain-of-function mechanism involving dysregulated protein-protein interactions. Similarly, altered molecular interactions may also lead to increased p.G447_G448insDG activity. In contrast, the partial loss-of-function associated with p.I126S was due to impaired protein stability, DNA binding, protein phosphorylation and subcellular distribution. These results support that moderate and variable FOXC1 transactivation changes are associated with moderate goniodysgenesis, dominant glaucoma and remarkable phenotypic variability.
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Registered trials
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