Novel β-Crystallin Gene Mutations in Chinese Families With Nuclear Cataracts

Objective To investigate the molecular genetic background in families with nuclear congenital cataract. Methods Family history and clinical data were recorded. Ten candidate genes were screened for causative mutations. 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 20 Chinese families with hereditary nuclear congenital cataract revealed 3 novel mutations. Two of these mutations (V146M and I21N) affected βB2-crystallin ( CRYBB2 ). One mutation (R233H) was detected in βB1-crystallin ( CRYBB1 ). These mutations cosegregated with all affected individuals and were not observed in unaffected family members or the 150 healthy unrelated individuals. Conclusions The CRYBB2 gene was shown to be another causative gene associated with congenital cataract and microcornea. Three novel mutations in β-crystallin genes ( CRYB ) were detected in Chinese families with nuclear autosomal dominant congenital cataracts, which underscores the genetic heterogeneity of this condition. Clinical Relevance Studying the genetics of nuclear cataracts is helpful for better understanding the pathophysiologic mechanisms that underlie this phenotype and for better disease management. This study helps expand the genotype of nuclear cataract and microcornea.