Mapping of an Autosomal Dominant Late-Onset Retinal Degeneration (L-ORD) Gene

Abstract

Abstract: : Purpose: To map the gene for Late-Onset Retinal Degeneration (L-ORD), an autosomal dominant disorder characterised by abnormal dark adaptation, central and peripheral visual loss in the sixth decade, and thick, lipid-rich sub-RPE deposits resembling those in age-related macular degeneration and Sorsby fundus dystrophy. Methods: Four L-ORD kindreds were clinically characterised and samples obtained for DNA extraction. A whole genome scan was carried out with markers at 10 cM intervals and further markers analysed in regions of interest. The results were analysed using two- and multi-point linkage programs (LINKAGE) assuming full penetrance for those examined over the age of 50. Results: Linkage analysis of a single extended pedigree identified a locus in chromosomal region 11q23, with a maximum LOD score of 6.77. The L-ORD candidate region was flanked by D11S4127 and D11S4094, defining a region of approximately 5.3 Megabases, containing at least 40 genes. This region was excluded in two of the four L-ORD families. Conclusions: The results show that one L-ORD locus maps to chromosomal region 11q23 and that L-ORD is genetically heterogeneous.

Keywords: retinal degenerations: hereditary • gene mapping • age-related macular degeneration