FOXE3 mutations: genotype-phenotype correlations.

Area of Science:

• Ophthalmology
• Genetics
• Developmental Biology

Background:

• Microphthalmia and anophthalmia (MA) are severe congenital eye disorders often with genetic origins.
• Over 30 genes are implicated in MA, each explaining a small fraction of cases.
• FOXE3 mutations have been associated with various ocular anomalies, including anterior segment dysgenesis and MA, with both dominant and recessive inheritance patterns.

Purpose of the Study:

• To investigate the role of FOXE3 gene mutations in a cohort of patients with MA.
• To analyze the spectrum of FOXE3 mutations and their correlation with ocular phenotypes and inheritance patterns.
• To enhance understanding of FOXE3's contribution to eye development and associated disorders.

Main Methods:

• Clinical examination and genetic analysis of 8 individuals with MA phenotypes.
• Identification and characterization of FOXE3 mutations, including novel variants.
• Systematic literature review of previously reported FOXE3 mutations in ocular anomalies.

Main Results:

• Seven out of eight patients with MA harbored biallelic recessive FOXE3 mutations, with two novel mutations identified (p.(Ala78Thr) and p.(Arg104Cys)).
• One patient presented with a heterozygous recessive FOXE3 mutation (p.(Arg90Leu)).
• Literature review revealed a correlation between FOXE3 mutation type, inheritance pattern (dominant vs. recessive), and the severity of the ocular phenotype.

Conclusions:

• FOXE3 mutations are a significant genetic cause of MA, exhibiting diverse mutation types and inheritance patterns.
• The genotype-phenotype correlation in FOXE3-related eye anomalies is complex and influences disease presentation.
• Understanding these genetic underpinnings is crucial for improved diagnosis, genetic counseling, and the development of targeted therapies for eye developmental disorders.