Purpose: Congenital cataract is a fundamental cause of blindness throughout the world. A large multi-generational family in northern China was investigated to determine the genetic cause of a progressive autosomal dominant congenital cataract.
Methods: Slit-lamp photography was conducted to provide definite data for cataract diagnosis. A genome wide scan, linkage analysis, and haplotype analysis were performed to shield the linkage region on the chromosome. BFSP2 was investigated by direct sequencing and detection of fluorescent labeled polymerase chain reaction (PCR) products.
Results: Two-point linkage analysis mapped this autosomal dominant congenital cataract (ADCC) locus to D3S1292 in 3q22.1 with a LOD score Zmax=3.99 (theta=0.00). Haplotype analysis located the cosegregating region between marker D3S1551 and D3S3617. In this region, BFSP2 is a powerful candidate gene. Direct sequencing identified the cosegregating E233del mutation in exon 3 of BFSP2. This mutation was not detected in 100 unrelated controls.
Conclusions: The E233del mutation in BFSP2 is the cause of the cataract phenotype in this pedigree. The progressive phenotype has provided more evidence for the heterogeneity of congenital cataract caused by BFSP2 mutations and for the important role BFSP2 plays in cataract formation.