Insights Into the FOXE3 Transcriptional Network and Disease Mechanisms From the Investigation of a Regulatory Variant Driving Complex Microphthalmia.

ABSTRACT:

Purpose

FOXE3 encodes a highly conserved, lens-enriched transcription factor essential for eye development. Biallelic mutations in FOXE3 are associated with a spectrum of ocular anomalies, ranging from congenital cataracts to complex microphthalmia (CM), with severity and penetrance correlating with genotype. This study aimed to investigate the regulatory landscape of FOXE3 and its contribution to CM.

Methods

In a patient with CM, a truncating FOXE3 variation (p.Cys240*) was identified alongside a second, trans-acting regulatory variant (rv: rs745674596G>A) located 3 kb upstream of FOXE3. To investigate its functional impact, mouse models were generated carrying either the rv or a frameshift (fs) mutation in homozygosity (Foxe3rv/rv, Foxe3fs/fs) or in compound heterozygosity

SUBMITTER: Plaisancie J 

PROVIDER: S-EPMC12383885 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature