Progressive sutural cataract associated with a BFSP2mutation in a Chinese family

[摘要] Purpose: To identify the mutation underlying the segregationof progressive sutural congenital cataracts in a four-generation Chinesepedigree.Methods: Genomic DNA was extracted from the peripheral bloodsamples of members of the pedigree. A genome-wide scan was performedusing microsatellite markers spaced at about 10 cM intervals. Linkageanalysis was carried out using a Linkage software package. Tenadditional microsatellite markers for the positive region were selectedfor precise targeting, and haplotype data were processed using Cyrillicsoftware to define the region of the disease gene. Mutation detectionwas carried out by sequencing candidate genes.Results: Significant evidence of linkage was obtained atmarker D3S1279 (LOD score [Z] =2.32, recombination fraction[θ]=0.0). Precise targeting and haplotype analysis traced thedisease gene to a 38.6 cM region bounded by D3S1267 and D3S1614 at3q21.1- q26.2 near BFSP2, which encodes a lens-specific beadedfilament protein. Sequencing results revealed a 3-bp deletion ofnucleotides 696-698 (GAA) in exon 3 of BFSP2, which is predicted tocause an in-frame deletion of glutamic acid residue 233 from thepolypeptide encoded by the mutant gene. This deletion was seen neitherin any unaffected member of the family nor in 50 unrelated controlindividuals.Conclusions: We observed progressive isolated suturalcataract associated with a deletion mutation of the BFSP2 gene in aChinese pedigree. It highlights the physiological importance of thebeaded filament protein and supports the role of BFSP2 in humancataract formation.

[学科分类] 生物化学/生物物理