Congenital cataract is a major cause of visual impairment and childhood blindness. The solubility and stability of crystallin proteins play critical roles in maintaining the optical transparency of the lens during the life span. Previous studies have shown that approximately 8.3%-25% of congenital cataracts are inherited, and mutations in crystallins are the most common. In this study, we attempted to identify the genetic defect in a four-generation family affected with congenital cataracts. The congenital cataract phenotype of this four-generation family was identified as membranous cataract by slit-lamp photography. Mutation screening of the candidate genes detected a heterozygous c.465G->C change in the exon6 of the betaB2-crystallin gene (CRYBB2) in all family members affected with cataracts, resulting in the substitution of a highly conserved Tryptophan to Cystine (p.W151C). The mutation was confirmed by restriction fragment length polymorphism (RFLP) analysis and found that the transition resulted in the absence of a BslI restriction site in the affected members of the pedigree. The outcome of PolyPhen-2 and SIFT analysis predicted that this W151C mutation would probably damage to the structure and function of betaB2-crystallin. Wild type (wt) and W151C mutant betaB2-crystallin were expressed in human lens epithelial cells (HLECs), and the fluorescence results showed that Wt-betaB2-crystallin was evenly distributed throughout the cells, whereas approximately 34.7% of cells transfected with the W151C mutant betaB2-crystallin formed intracellular aggregates. Taken together, these data suggest that the missense mutation in CRYBB2 gene leads to progressive congenital membranous cataract by impacting the solubility and function of betaB2-crystallin. © 2013 Chen et al.
W., C., X., C., Z., H., H., L., F., Z., L., L., … S., Y. (2013). A missense mutation in CRYBB2 leads to progressive congenital membranous cataract by impacting the solubility and function of betaB2-crystallin. PLoS ONE, 8(11), e81290. https://doi.org/http://dx.doi.org/10.1371/journal.pone.0081290