ArticleThe Journal of clinical investigation2014
Mutation of FOXC1 and PITX2 induces cerebral small-vessel disease.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 149 citations in OpenAlex.
- Identification of additional risk loci for stroke and small vessel disease: a meta-analysis of genome-wide association studies.The Lancet. Neurology · 2016Pooled it
- Cross-phenotype and cross-species integrative genomic prioritization of FOXF2 and FOXC1 at a cerebral small vessel disease locus.Functional & integrative genomics · 2026Article
- Article
- Biomarker advancements in cerebral small vessel disease: An overview.Neural regeneration research · 2026Article
- Automated analysis of zebrafish vascular networks using the VISTA-Z pipeline.Scientific reports · 2026Article
- FOXC1 expression and radiological predictors of peritumoral brain edema in meningiomas.Journal of neuro-oncology · 2026Article
- A case of Axenfeld-Rieger syndrome with neuroradiological abnormalities.Radiology case reports · 2025Article
- Optic disc morphology in congenital glaucoma.Eye (London, England) · 2025Article
- Genetic Architecture of Ischemic Stroke: Insights from Genome-Wide Association Studies and Beyond.Journal of cardiovascular development and disease · 2025Review
- Review
- Reactivation of an embryonic cardiac neural crest transcriptional profile during zebrafish heart regeneration.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Metabolism-Mediated FGF5 Association with Stroke: Based on Mendelian Randomization and Bioinformatics Analysis.Journal of multidisciplinary healthcare · 2025Article
- FOXC1 and retinopathy: targeting molecular mechanisms in retinal blood vessel growth.Expert opinion on therapeutic targets · 2024Article
- Impact of Intrauterine Insults on Fetal and Postnatal Cerebellar Development in Humans and Rodents.Cells · 2024Review
- Cellular heterogeneity and dynamics of the human uterus in healthy premenopausal women.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Novel Mutation of FOXC1 (P136L) in an Axenfeld-Rieger Syndrome Patient With a Systematized Delusion of Jealousy: A Case Report and Literature Review.Molecular genetics & genomic medicine · 2024Review
- Cerebral small vessel disease was associated with the prognosis in ischemic stroke with atrial fibrillation.CNS neuroscience & therapeutics · 2024Article
- Pleiotropy in FOXC1-attributable phenotypes involves altered ciliation and cilia-dependent signaling.Scientific reports · 2024Article
- Cerebral Vascular Toxicity after Developmental Exposure to Arsenic (As) and Lead (Pb) Mixtures.Toxics · 2024Article
- FOXC1 regulates endothelial CD98 (LAT1/4F2hc) expression in retinal angiogenesis and blood-retina barrier formation.Nature communications · 2024Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 4 countries.
Funding
Abstract
Patients with cerebral small-vessel disease (CSVD) exhibit perturbed end-artery function and have an increased risk for stroke and age-related cognitive decline. Here, we used targeted genome-wide association (GWA) analysis and defined a CSVD locus adjacent to the forkhead transcription factor FOXC1. Moreover, we determined that the linked SNPs influence FOXC1 transcript levels and demonstrated that patients as young as 1 year of age with altered FOXC1 function exhibit CSVD. MRI analysis of patients with missense and nonsense mutations as well as FOXC1-encompassing segmental duplication and deletion revealed white matter hyperintensities, dilated perivascular spaces, and lacunar infarction. In a zebrafish model, overexpression or morpholino-induced suppression of foxc1 induced cerebral hemorrhage. Inhibition of foxc1 perturbed platelet-derived growth factor (Pdgf) signaling, impairing neural crest migration and the recruitment of mural cells, which are essential for vascular stability. GWA analysis also linked the FOXC1-interacting transcription factor PITX2 to CSVD, and both patients with PITX2 mutations and murine Pitx2-/- mutants displayed brain vascular phenotypes. Together, these results extend the genetic etiology of stroke and demonstrate an increasing developmental basis for human cerebrovascular disease.
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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.