Mutation Screen in CRYBB Genes in 379 Patients With Age-Related Macular Degeneration

Abstract

Purpose: : βγ-Crystallins are a superfamily (CRYBA1-A4, CRYBB1-3, CRYGA-F) of small heat shock proteins expressed primarily in the ocular lens, and in low levels in other tissues. Since CRYBB1 and CRYBB2 are common drusen proteins in age-related macular degeneration (AMD) eyes, we investigated CRYBB1 and CRYBB2 as candidate genes for AMD.

Methods: : All five coding exons of each CRYBB1 and CRYBB2 were screened for mutations in 379 unrelated patients with AMD using a combination of exon-by-exon SSCP and direct genomic sequencing. A previously reported pseudogene, CRYBB2P1, was detected and excluded.

Results: : Five sequence changes (Gly25Glu, Arg60Thr, IVS3+16C->A, Arg110Cys and IVS4+15G->A) were identified in CRYBB1. Gly25Glu had an allele frequency of 0.13% in patients and was absent in 381 age-matched normal controls. Both the Arg60Thr and IVS4+15G->A changes were identified in one age-matched normal control each, but absent in patients. IVS3+16C->A was identified heterozygously with an allele frequency of 4.62% in patients. Arg110Cys had an allele frequency of 0.79% in patients and 0.26% in age-matched controls. Two sequence changes (IVS2+24G->T and IVS4-22A->G) were identified in CRYBB2. Both intron changes were identified with an allele frequency of 0.13%.

Conclusions: : We report seven sequence changes in CRYBB in patients with AMD. However, we cannot associate these changes with AMD and they are likely nonpathogenic polymorphisms.

Keywords: genetics • gene screening • age-related macular degeneration