EPHA2 biallelic disruption causes syndromic complex microphthalmia with iris hypoplasia

Area of Science:

• Genetics
• Ophthalmology
• Developmental Biology

Background:

• Congenital ocular malformations like microphthalmia, coloboma, and anterior segment dysgeneses result from disruptions in ocular development.
• These defects arise from genetic heterogeneity, involving numerous genes, with aniridia often linked to PAX6 mutations.

Observation:

• A patient presented with bilateral microphthalmia, congenital cataract, corneal dystrophy, and iris hypoplasia, alongside extra-ocular features.
• Genetic analysis of 119 ocular development genes identified two truncating variants in the EPHA2 gene.

Findings:

• This case represents the first report of complex anterior segment dysgenesis caused by biallelic EPHA2 mutations.
• EPHA2 mutations are typically associated with isolated dominant congenital cataracts, but this expands the observed phenotype.

Implications:

• The EPHA2 gene should be considered in genetic testing for aniridia when PAX6 testing is negative, as phenotypes can overlap.
• This study broadens the spectrum of EPHA2-associated ocular disorders and suggests a potential interaction between PAX6 and EPHA2.
• Further research is warranted to investigate the genotype-phenotype correlation and the potential PAX6-EPHA2 interaction in ocular development.