A novel p.G112E mutation in BFSP2 associated with autosomal dominant pulverulent cataract with sutural opacities.

PURPOSE: To identify the genetic defect in a Chinese family with bilateral pulverulent sutural cataract.

MATERIALS AND METHODS: A three-generation family with congenital cataract was recruited in the study. The study protocol followed the principles of the Declaration of Helsinki. Detailed family history and clinical data were recorded. Genomic DNA was extracted from peripheral blood leukocytes. Candidate gene sequencing was performed to identify the disease-causing mutation. The effects of amino acid changes on the structure and function of proteins were predicted by bioinformatics analysis.

RESULTS: All affected individuals presented pulverulent opacities in the embryonal nucleus and sutures. Direct candidate gene sequencing revealed a heterozygous c. 335 G>A variation in the beaded filament structural protein 2(BFSP2) gene, which resulted in the replacement of a highly conserved glycine by glutamic at codon 112 (p. G112E). Haplotype analysis indicated that the affected members shared a common haplotype with markers near BFSP2. This mutation co-segregated with all affected individuals and was not observed in unaffected members or in 120 ethnically matched controls. Bioinformatic analyses confirmed that the mutation altered the hydrophobic and secondary structure of the protein around the substitution site.

CONCLUSIONS: We report a novel mutation (p.G112E) in the BFSP2 gene, underscoring the physiological importance of the beaded filament protein and supporting its role in human cataract formation.