Characterization of a novel mutation in the CRYBB2 gene associated with autosomal dominant congenital posterior subcapsular cataract in a Chinese family

PURPOSE: To identify the underlying genetic defect in four generations of a Chinese family affected with bilateral congenital posterior subcapsular cataracts. METHODS: Clinical data from patients in the family were recorded by slit-lamp photography. Genomic DNA samples were extracted from peripheral blood of the pedigree members. Mutation screening was performed in the candidate gene by bidirectional sequencing of the amplified products. The mutation was verified by restriction fragment length polymorphism (RFLP) analysis. RESULTS: The congenital cataract phenotype of the pedigree was identified as posterior subcapsular by slit-lamp photography. Sequencing of the candidate genes detected a heterozygous c.5C→T change in the coding region of the βB2-crystallin gene (CRYBB2), resulting in the substitution of a highly conserved alanine to valine (p. A2V). All nine family members affected with cataracts were positive for this change, but it was not observed in any of the unaffected members of the family. The transition resulted in the loss of a HaeIII restriction site in the affected members of the pedigree, which was present in the unaffected family members and in all of the 100 unrelated individuals tested. CONCLUSIONS: This study has identified a novel CRYBB2 gene mutation, resulting in the amino substitution p. A2V in a Chinese family with posterior subcapsular congenital cataracts. This mutation is probably the causative lesion for the observed phenotype in this family.