Variants and genotype-phenotype correlation of CRYBB2 gene in eight Chinese families with congenital cataract and other congenital ocular anomalies

The aim of this study is to explore the clinical phenotypes of congenital cataract caused by CRYBB2 variants and the surgical prognosis, so as to establish the association between the CRYBB2 gene and the genetic phenotypes of congenital cataract, and provide a reference for genetic counseling and treatment prognosis. A total of 120 families with congenital cataract were included in this study. Whole exome sequencing and Sanger sequencing were carried out to detect and confirm genetic variants. Bioinformatics analysis was employed to evaluate the occurrence frequency, conservation, pathogenic potential, and hydrophobicity of the mutated amino acids. Families with CRYBB2 gene variations were screened out for further analysis. Afterward, bioinformatic analysis through several computational predictive programs was performed to assess impacts of variations on protein structure and function. Eight pathogenic or likely pathogenic CRYBB2 variants were identified in eight unrelated families, including three novel variants (c.355G > C:p.G119R, c.462C > A:p.Y154*, c.84_89del: p.Q28_G29del) and five reported variants (c.355G > A:p.G119R, c.436G > A:p.V146M, c.463 C > T:p.Q155*, c.481G > A:p.G161R, c.563G > C:p.R188P). The associated cataract phenotypes included total cataract, cerulean cataract, and perinuclear cataract. Among the study cohort, two patients presented with both microphthalmia and microcornea, while one patient exhibited microphthalmia accompanied by posterior capsule coloboma (PCD). This study expands the mutational spectrum of CRYBB2 and highlights its association not only with congenital cataract but also with ocular developmental abnormalities such as microphthalmia and microcornea. These findings improve understanding of CRYBB2 -related phenotypic diversity and provide valuable information for molecular diagnosis and genetic counseling.