FOXC1 -associated phenotypes in humans may not always exhibit corneal neovascularization

Abstract

The transcription factor gene FOXC1 has been implicated with Axenfeld–Rieger syndrome (ARS) in humans. Mutations in this gene have been suggested to contribute to the mechanism leading to developmental defects in the anterior chamber of the eye. In PNAS, Seo et al. (1) demonstrated that mutations in FOXC1 led to corneal angiogenesis in mice and in anterior segment anomalies like ARS in humans. Although the data on mice are very convincing, we provide a different perspective based on our observations in two different patient cohorts with FOXC1 mutations. Our screening of patients (n = 10) with Axenfeld–Rieger anomaly (ARA) for FOXC1 mutations did not reveal any form of corneal neovascularization among the heterozygous mutation carriers (2). We also screened the FOXC1 gene in a large cohort (n = 210) of another related disease, primary congenital glaucoma (PCG) without any anterior segment anomalies, and, similarly, the mutations carriers were devoid of any corneal neovascularization as observed in our ARA cohort (3). Interestingly, the results were consistent across PCG cases that harbored heterozygous alleles of FOXC1 alone or in combination with an accompanying allele of CYP1B1.