Whole Exome Sequencing Reveals New Genetic Insights into Age-Related typical Posterior Polar Cataract: A Case Report

Cataract refers to lens opacity that includes blurred, cloudy, or double vision. In cataract patients, posterior polar cataract (PPC) has a surgical challenge for all ophthalmologists due to the dense adherence to the posterior capsule or pre-existing posterior capsular dehiscence having the risk of posterior capsular rupture, nucleus drop, aphakia, and vitreous prolapse. Molecular genetics and pathogenesis of PPC is not well known. So far, only four genes including EPHA2 , CRYAB, CHMP4B , and PITX3 have been identified in PPC. PPC is also observed in several syndromic cases of eye disease like Anterior segment dysgenesis 1, Primrose syndrome, familial Danish, Retinitis pigmentosa 74, which are caused by mutation in specific genes. In the present study, we identified the 11 genetic variants by Whole exome sequencing (WES) in typical senile PPC patient. These genetic variants were observed in 11 different genes, which were ABCC6:c.1171A > G, MYRF:c.872G > A, MYO7A:c.6362C > T, IFT122:c.1219C > T, PNPT1:c.959C > T, VGLL4:c.266C > T, CPAMD8:c.1205G > A, CTU2:c.697C > T, EPB41:c.1226G > A, ZBTB40:c.911C > T , and JAK1:c.1726G > A. Previously, none of the variants and genes were reported in PPC patients. However, most of these genes are found in association of other syndromic cases of eye diseases. On the basis of ACMG Classification, we suggests that ABCC6:c.1171A > G is the most strong pathogenic genetic variant, followed by MYRF:c.872G > A causing PPC phenotype in North Indian patient. This study also reports the association novel genes, EPB41 (c.1226G > A) and ZBTB40 (c.911C > T) which have not been found in association of any eye disorder or PPC phenotypes.