Abstract
Abstract: :
Purpose: To determine the clinical phenotype, disease progression and linkage analysis in a large pedigree with exudative age–related macular degeneration (AMD). Methods: A large pedigree with exudative AMD was identified 13 years ago from clinic attendances. Members from the 2 most elderly generations were examined. The phenotype was clinically severe, of late onset with disease expression being similar in all affected family members. At that time 6 of 12 siblings were found to be affected, but none of the second generation showed signs of disease. The second generation members have recently been re–examined to establish any change in disease status with a view to defining disease progression within the pedigree, refining the phenotype and detecting linkage in this family. All available members had standard ophthalmological examination with stereo digital fundus photography. Retinal photographs were graded independently according to the Rotterdam "Classification of mutually exclusive stages of ARM". A genome–wide search for linkage was undertaken in all available family members, with linkage analysis limited to affecteds only. DNA was typed for 400 marker loci at intervals of approximately 10 cM using the ABI linkage mapping set MD10. Alleles were sized using Genotyper and scored with C–allele software. Linkage analysis was performed using FASTLINK. Results: Twenty–three of 30 available 2nd generation members attended for clinical re–evaluation. DNA and clinical information was available on 7 of the 1st generation members from examination 12 years ago, 6 of whom are now deceased. Eleven of 23 second generation members reviewed were now found to be affected. Linkage analysis indicates a region of significant linkage which is currently being refined. Conclusions: We present the results of the phenotype and linkage analysis in an autosomal dominant form of AMD with variable penetrance. Further studies are underway to identify the causative gene and to test association of this locus in a cohort of AMD patients. It is hoped that the results from this family will shed light on the pathogenesis of exudative AMD.
Keywords: age–related macular degeneration • gene mapping • candidate gene analysis