title: A missense mutation in CRYBB2 leads to progressive congenital membranous cataract by impacting the solubility and function of βB2-crystallin.
abstract: 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 βB2-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 βB2-crystallin. Wild type (wt) and W151C mutant βB2-crystallin were expressed in human lens epithelial cells (HLECs), and the fluorescence results showed that Wt-βB2-crystallin was evenly distributed throughout the cells, whereas approximately 34.7% of cells transfected with the W151C mutant βB2-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 βB2-crystallin.
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Weirong
authors: W
authors: Chen
authors: Xiaoyun
authors: X
authors: Chen
authors: Zhengmao
authors: Z
authors: Hu
authors: Haotian
authors: H
authors: Lin
authors: Fengqi
authors: F
authors: Zhou
authors: Lixia
authors: L
authors: Luo
authors: Xinyu
authors: X
authors: Zhang
authors: Xiaojian
authors: X
authors: Zhong
authors: Ye
authors: Y
authors: Yang
authors: Changrui
authors: C
authors: Wu
authors: Zhuoling
authors: Z
authors: Lin
authors: Shaobi
authors: S
authors: Ye
authors: Yizhi
authors: Y
authors: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002386:Cataract / Q000151:congenital* / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002648:Child; D019295:Computational Biology; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007908:Lens, Crystalline / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D066329:Protein Aggregates; D016415:Sequence Alignment; D012995:Solubility; D038206:beta-Crystallin B Chain / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D066329:Protein Aggregates; D038206:beta-Crystallin B Chain; C113634:beta-crystallin B2