Identification and functional characterization of a novel CRYBB1 deletion mutation causing autosomal dominant congenital cataract in a Chinese family.

BACKGROUND

Congenital cataract is a leading cause of childhood blindness worldwide, often caused by genetic mutations that disrupt lens transparency. This study aimed to investigate the molecular mechanisms by which crystallin beta B1 (CRYBB1) mutation contributes to cataract formation.

METHODS

We identified a novel heterozygous deletion mutation (c.688_733del) in CRYBB1 in a Chinese Han family with autosomal dominant congenital nuclear cataract. Functional assays were conducted in human lens epithelial cells to assess effects on cell proliferation, migration, cell cycle progression, apoptosis, and oxidative stress. Mechanistic studies evaluated activation of mitochondrial apoptosis pathways.

RESULTS

The c.688_733del mutation disrupts conserved domains essential for βB1-crystallin protein folding and stability. Mutant protein impaired cell proliferation and migration, induced G1 cell cycle arrest, and significantly increased apoptosis. Elevated intracellular reactive oxygen species were observed, triggering mitochondrial apoptosis via Bax/Bcl-2 imbalance and caspase-3 activation.

CONCLUSION

Oxidative stress-mediated apoptosis is a key pathogenic mechanism in CRYBB1-related cataractogenesis. These findings expand the CRYBB1 mutational spectrum and provide a molecular basis for future diagnostic and therapeutic strategies.