Mutation Screen in the CLUL1 Gene in 380 Patients With Age–Related Macular Degeneration

Abstract

Abstract: : Purpose: Clusterin (CLU) is expressed in many tissues and appears to function in a wide range of chaperone processes including membrane recycling and neurodegeneration. A retina–specific clusterin–like protein (CLUL1) was recently shown to be expressed in cone photoreceptor cells. Since CLUL1 is a common drusen protein in age–related macular degeneration (AMD) eyes, we investigated CLUL1 as a candidate gene for AMD. Methods: All eight coding exons have been screened for mutations in 380 unrelated patients with AMD using exon–by–exon SSCP. Variant bands detected by SSCP were further analyzed by direct genomic sequencing. Results: Two sequence changes (IVS2+18C→T and IVS8+10insTGCCTGGTTAGGAA) were identified in CLUL1. The IVS2+18C→T change had an allele frequency of 49.6% in patients and 42.8% in age–matched normal controls. IVS8+10(14–bp ins) was identified heterozygously in one patient with AMD and two normal controls, all of African American decent. The minor allele frequency for this sequence change is 0.2% in patients and 0.6% in normals. Conclusions: We report two sequence changes in CLUL1 in patients with AMD; however, we were unable to associate these changes with disease. Both changes are likely nonpathogenic polymorphisms. Our data suggests that mutations in this gene are rare. It is possible that pathogenic mutations in this gene cause a form of retinal degeneration not included in our patient set.

Keywords: candidate gene analysis • gene screening • retinal degenerations: hereditary