Whole-exome sequencing for identification of genetic changes in adult-onset posterior polar cataract

Posterior polar cataract (PPC), a rare congenital cataract, is characterized by subcapsular opacities in the lens affecting vision and posing surgical challenges. Genetic heterogeneity exists, though several genes are implicated in its pathogenesis. This study reports on the genetic profile of late-onset PPC cases and identifies variations specific to posterior capsular rupture (PCR) during surgery.

Detailed clinical and genetic history was documented from 100 clinically diagnosed PPC patients and 100 controls. Whole-exome sequencing (WES) was performed in 30 patients and 15 controls, and pathogenic variants were validated in 70 patients and 85 controls by Sanger sequencing.

Bilateral PPC was seen in 58%, sporadic cases were 61%, while 39% had a family history. Phacoemulsification was performed on 89 patients, with 12 patients experiencing PCR. Analysis revealed novel and reported variations in the genes - CRYAB (c.328T>G; p.C110G), CRYGB - (c.331A>C; p.I111L), (c.44G>A; p.R15H), CRYBG3 - ( c.1115C>T; p.S372F), CRYBA1 - (c.516A>C; p.G172H), along with EPHA2 (c.1114 G>A; p.E372K), GJA3- (c.895C>A; p.L299M), and PITX3 (c.285C>T; p.I95I). CRYBG3 and GJA3 variations were common among the PCR cases.

Results indicate genetic heterogeneity with no mutation hotspots, and the absence of PITX3 variations in our patient cohort is interesting. The study highlights the importance of mutation screening and genotype-phenotype relationships and underscores the importance of accurate diagnosis for enhanced cataract care and management. Subsequent functional studies on the role of these genes may help in understanding normal lens development and provide insights for advanced surgical approaches.