Congenital polymorphic cataract associated with a G to A splice site mutation in the human beta-crystallin gene CRYβA3/A1

PURPOSE: To identify the underlying genetic defect in four generations of a Chinese family affected with bilateral congenital polymorphic cataracts. METHODS: Family history and clinical data were recorded. The phenotype was documented using slit-lamp photography. Genomic DNA samples were extracted from peripheral blood of family members. Candidate genes were amplified using polymerase chain reaction (PCR) and screened for mutations on both strands using bidirectional sequencing. RESULTS: Affected individuals exhibited variable opacities in the embryonic nucleus, sutures, and peripheral cortical opacities. The phenotype for this family was identified as polymorphic. Direct sequencing revealed a splice site mutation (c.215+1G>A) at the first base of intron 3 of the crystallin beta A3/A1 (CRYBA3/A1) gene. This mutation co-segregated with all affected individuals in the family and was not found in unaffected family members or in 100 unrelated controls. CONCLUSIONS: Our results identified a recurrent c.215+1G>A mutation in CRYBA3/A1 in a polymorphic congenital cataract family, summarized the variable phenotypes among the patients, which expanded the phenotypic spectrum of congenital cataract in a different ethnic background, and suggested a mechanism that influences cataractogenesis.