Studies have established that congenital cataract is the major cause of blindness in children across the globe. The β-crystallin protein family is the richest and most soluble structural protein in the lens. Their solubility and stability are essential in maintaining lens transparency. In this study, we identified a novel βB2 mutation W151R in a rare progressive cortical congenital cataract family and explored its pathogenesis using purified protein and mutant related cataract-cell models. Due to its low solubility and poor structural stability, the βB2 W151R mutation was prone to aggregation. Moreover, the W151R mutation enhanced the exposure of the hydrophobic side chains in the fourth Greek Key motif, which were readily degraded by trypsin. However, upon the administration of lanosterol, the negative effect of the W151R mutation was reversed. Therefore, lanosterol is a potential therapeutic option for cataracts.

研究表明，先天性白内障是导致全球儿童失明的主要原因。β-晶状体蛋白家族是晶状体中最丰富，最易溶的结构蛋白。它们的溶解性和稳定性对于保持镜片透明性至关重要。在这项研究中，我们在罕见的进行性皮质先天性白内障家族中鉴定了一个新的βB2突变W151R，并使用纯化的蛋白质和突变体相关的白内障细胞模型探讨了其发病机理。由于其低溶解度和较差的结构稳定性，βB2W151R突变易于聚集。此外，W151R突变增强了第四个希腊密钥基序中疏水侧链的暴露，后者容易被胰蛋白酶降解。然而，在施用羊毛甾醇后，W151R突变的负面作用被逆转。