Objective  To investigate the molecular genetic background in families with nuclear congenital cataract.
Methods  Family history and clinical data were recorded. Ten candidate genes sequencing were applied to find the causative mutation. Direct sequencing was performed to analyze the cosegregation of the genotype with the disease phenotype. Effects of amino acid changes on the structure and function of protein were predicted by bioinformatics analysis.
Results  Analyses of twenty Chinese families with hereditary nuclear congenital cataract revealed three novel mutations. Two of these affected the βB2-crystallin (CRYBB2), including V146M and I21N mutations. One mutation (R233H) was detected in βB1-crystallin (CRYBB1). These mutations co-segregated with all affected individuals and were not observed in unaffected or 150 normal unrelated individuals.
Conclusions  Our study provides CRYBB2 as another causative gene associated with congenital cataract and microcornea. Three novel mutations in β-crystallin genes (CRYB) are detected in Chinese families with autosomal dominant nuclear cataracts, which underscore the genetic heterogeneity of this condition.