Malattia leventinese: refinement of the genetic locus and phenotypic variability in autosomal dominant macular drusen

Abstract

PURPOSE: To study the phenotypic variability in patients inheriting the disease gene for malattia leventinese (dominant macular drusen) and refine the localization of the gene.METHODS: A family with dominant radial drusen was ascertained and studied with clinical examination and DNA linkage analysis. Inheritance of the disease gene was determined by DNA analysis and used to document the variability in phenotypic expression.RESULTS: Fifty family members were studied with fundus photography and genotyping. Linkage analysis showed that the disease in this family was linked to chromosome 2p16-21 with a maximum lod score of 3.72 at D2S2153. An affected patient with obligate recombinations allowed refinement of the disease interval to a 6.2-cM region between D2S2227 and D2S378. The phenotype of older affected patients varied from severe geographic atrophy or subretinal fibrosis to a single druse adjacent to the optic disk. Small and medium-sized, nonradial, and soft macular drusen seen in four older individuals in the family were not specifically associated with the disease haplotype.CONCLUSIONS: Refinement of the localization of the gene for malattia leventinese will facilitate its positional cloning. Genotypic documentation of the variable expression of the disease shows that a single, large, subretinal druse adjacent to the optic disk is consistent with inheritance of the disease gene. Soft macular drusen in low abundance were not specifically associated with inheritance of the disease gene. These results will facilitate the genetic counseling of patients with malattia leventinese. It is unknown what proportion of age-related macular degeneration arises from mutations in disease genes for dominant drusen.