PSMD3 gene mutations cause pathological myopia

Area of Science:

• Genetics
• Ophthalmology
• Molecular Biology

Background:

• Pathological myopia (PM) has known genetic influences, but its precise genetic underpinnings remain largely unknown.
• Understanding the genetic basis of PM is crucial for developing targeted therapies and interventions.

Purpose of the Study:

• To identify candidate gene mutations responsible for pathological myopia (PM) within a Chinese family.
• To investigate the potential molecular mechanisms contributing to PM pathogenesis.

Main Methods:

• Exome and Sanger sequencing were employed in a Chinese family and 179 sporadic PM cases.
• Gene expression was analyzed using RT-quantitative real-time PCR (RT-qPCR) and immunofluorescence.
• Apoptosis rates and myopia-related parameters in mutant mice were assessed.

Main Results:

• A novel PSMD3 variant (c.689T>C; p.F230S) was identified in a PM family, alongside a rare mutation (c.1015C>A; p.L339M) in sporadic cases.
• PSMD3 expression was confirmed in human eye tissue; mutations decreased its mRNA and protein levels, inducing retinal pigment epithelial cell apoptosis.
• Mutant mice exhibited significantly increased axial length (AL) compared to wild-type controls.

Conclusions:

• The study identified PSMD3 as a potential pathogenic gene associated with pathological myopia (PM) in a Chinese family.
• PSMD3 mutations may contribute to axial length elongation and the overall development of PM.